Annals of Internal MedicineT

In the ClinicT

Type 2 Diabetes
T
ype 2 diabetes (T2D) is a prevalent disease
that increases risk for vascular, renal, and
neurologic complications. Prevention and
treatment of T2D and its complications are para-
mount. Many advancements in T2D care have
emerged over the past 5 years, including Screening and Prevention
increased understanding of the importance of
early intensive glycemic control, mental health, Diagnosis and Evaluation
social determinants of health, healthy eating pat-
terns, continuous glucose monitoring, and the
benefits of some drugs for preventing cardiorenal Treatment
disease. This review summarizes the evidence sup-
porting T2D prevention and treatment, focusing
Practice Improvement
on aspects that are commonly in the purview of
primary care physicians.

CME/MOC activity available at Annals.org.

Physician Writers doi:10.7326/AITC202406180

Allison L. Crawford, MD, MS
Neda Laiteerapong, MD, MS This article was published at Annals.org on 11 June 2024.
The University of Chicago CME Objective: To review current evidence for screening, prevention, diagnosis,
Medical Center, Chicago, evaluation, treatment, and practice improvement for type 2 diabetes.
Illinois (A.L.C.)
University of Chicago, Chicago, Funding Source: American College of Physicians.
Illinois (N.L.)
Acknowledgment: The authors thank Sandeep Vijan, MD, author of the previous
version of this In the Clinic.
Disclosures: All relevant financial relationships have been mitigated. Disclosures
can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.
do?msNum¼M24-0758.

With the assistance of additional physician writers, the editors of Annals of

Internal Medicine develop In the Clinic using MKSAP and other resources of
the American College of Physicians.
In the Clinic does not necessarily represent official ACP clinical policy. For ACP
clinical guidelines, please go to www.acponline.org/clinical_information/
guidelines.
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 Type 2 diabetes (T2D) is among the impaired glucose tolerance (1). Diabetes
most common diseases encountered is a leading cause of vision loss, amputa-
by internal medicine physicians. Data tion, and end-stage renal disease in the
1. Centers for Disease Control from 2021 indicate that more than 38 United States and is a substantial risk fac-
and Prevention. National
Diabetes Statistics Report. million people in the United States tor for atherosclerotic disease, the leading
Accessed at www.cdc.gov/
diabetes/data/statistics- have diabetes and about 90% to 95% cause of morbidity, mortality, and expen-
report/index.html on 22 of them have T2D. Incidence is ex- ditures in persons with T2D (2). Although
November 2023.
2. Mangione CM, Barry MJ, pected to increase due to aging, the population-based cardiovascular risk fac-
Nicholson WK, et al; US
Preventive Services Task changing U.S. ethnic mix, and the in- tor (CVRF) control has improved since
Force. Screening for predia- creasing prevalence of obesity. An esti- 2000, only 1 in 5 U.S. adults achieve con-
betes and type 2 diabetes
in children and adoles- mated 8.7 million people have undiag- trol of hemoglobin A1c (HbA1c), blood
cents: US Preventive
Services Task Force recom- nosed diabetes, and 98 million (38% of pressure (BP), and cholesterol, and con-
mendation statement. U.S. adults) have prediabetes, defined trol is lower among young adults and
JAMA. 2022;328:963-967.
[PMID: 36098719] as impaired fasting glucose level or racial or ethnic minority populations (3).
3. Wang L, Li X, Wang Z, et al.
Trends in prevalence of dia-
betes and control of risk
factors in diabetes among
US adults, 1999–2018.
JAMA. 2021;326:1-13. Screening and Prevention
[PMID: 34170288]
4. Lind M, Imberg H, Whom should we screen for T2D? cians should offer or refer patients with
Coleman RL, et al.
Historical HbA1c values
Diabetes has a long asymptomatic phase prediabetes to effective preventive inter-
may explain the type 2 dia- during which some people develop ventions (5). Similarly, the U.S. Preventive
betes legacy effect: UKPDS
88. Diabetes Care. early complications, such as retinopathy Services Task Force (USPSTF) recom-
2021;44:2231-2237. or microalbuminuria. Early treatment of
[PMID: 34244332]
mends screening in adults with over-
5. American Diabetes T2D has been shown to improve out- weight and obesity every 3 years, as well
Association Professional
Practice Committee. 2. comes (4). Because early intervention as adults at increased risk for diabetes
Diagnosis and classification can delay development of T2D and/or
of diabetes: Standards of (Box: Risk Factors for T2D) (2).
Care in Diabetes—2024. its complications, screening is most likely
Diabetes Care. 2024;47:
to improve outcomes in adults with risk Strong evidence shows that intensive
S20-S42. [PMID:
38078589] factors for cardiovascular disease (CVD) glycemic control in people newly diag-
6. UK Prospective Diabetes
Study (UKPDS) Group. and adults for whom T2D confers a nosed with T2D improves long-term out-
Effect of intensive blood-
glucose control with higher risk for complications (Box: Risk comes (6–8), although some of these
metformin on Factors for T2D). The 2024 American benefits may take at least a decade to
complications in
overweight patients with Diabetes Association (ADA) guidelines appear (6–8). Moreover, the benefits of
type 2 diabetes (UKPDS
34). Lancet. 1998;352:854- recommend that all adults be screened early intensive glycemic control seem to
865. [PMID: 9742977] beginning at age 35 years (or before if extend beyond the period of intensive
7. UK Prospective Diabetes
Study (UKPDS) Group. they have risk factors, such as elevated control, a phenomenon called “legacy
Intensive blood-glucose
control with sulphonylureas body mass index [BMI]) and that clini- effects” or “metabolic memory” (4, 9, 10).
or insulin compared with
conventional treatment and
risk of complications in
patients with type 2
diabetes (UKPDS 33).
Lancet. 1998;352:837-853.
[PMID: 9742976]
Risk Factors for T2D
8. Holman RR, Paul SK, • Age ≥35 years
Bethel MA, et al. 10-year • Black/African American, Hispanic/Latino, Asian, Pacific Islander, or Native American race/
follow-up of intensive glu-
cose control in type 2 dia- ethnicity
betes. N Engl J Med. • First-degree relative with T2D
2008;359:1577-1589. • Physical inactivity
[PMID: 18784090]
• Smoking
9. Lachin JM, Nathan DM;
DCCT/EDIC Research Group. • History of gestational diabetes or delivery of infant weighing ≥9 lb
Understanding metabolic • Overweight (BMI ≥25 kg/m2 [≥23 kg/m2 in Asian persons])
memory: the prolonged • Polycystic ovary syndrome
influence of glycemia dur-
ing the Diabetes Control
• HIV
and Complications Trial • Prediabetes, impaired glucose tolerance, or impaired fasting glucose
(DCCT) on future risks of • CVD, hypertension, dyslipidemia, or other features of metabolic syndrome
complications during the • Use of thiazide diuretics (chlorthalidone), first- and second-generation b-blockers (metoprolol,
study of the Epidemiology
of Diabetes Interventions propranolol), high doses of calcium-channel blockers (nifedipine, diltiazem), high-potency sta-
and Complications (EDIC). tins (atorvastatin, rosuvastatin), glucocorticoids, HIV medications, atypical antipsychotics, oral
Diabetes Care. contraceptives
2021;44:2216-2224.
[PMID: 34548284]

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Can T2D be prevented? 7% weight loss reduced T2D incidence
T2D can be prevented through inten- from 29% to 14% over 3 years (relative
10. Laiteerapong N, Ham SA,
sive changes in diet and exercise and risk [RR], 0.42 [95% CI, 0.34 to 0.52]) ver- Gao Y, et al. The legacy
treatment with metformin. The USPSTF sus placebo (12). A smaller reduction effect in type 2 diabetes:
impact of early glycemic
recommends lifestyle interventions in was noted in patients assigned to met- control on future compli-
cations (The Diabetes &
patients with prediabetes because evi- formin (850 mg twice daily) (29% vs. Aging Study). Diabetes
dence suggests a moderate reduction 22%; RR, 0.69 [CI, 0.57 to 0.83]) versus Care. 2019;42:416-426.
[PMID: 30104301]
in progression to T2D and improve- placebo (12), although not among peo- 11. Krist AH, Davidson KW,
Mangione CM, et al; US
ments in other CVRFs (11). High-quality ple aged 60 years or older. Both treat- Preventive Services Task
randomized controlled trials (RCTs) ment groups regained some weight Force. Behavioral counsel-
ing interventions to pro-
suggest diet and exercise can lead to over time; incidence of T2D at 10 years mote a healthy diet and
physical activity for cardio-
modest weight loss (generally 5% to was 34% and 18%, respectively (13). vascular disease preven-
tion in adults with
7%) that mitigates progression to T2D
Thus, clinicians should counsel patients cardiovascular risk factors:
among adults with overweight or obe- US Preventive Services
to reduce caloric intake by 500 to 1000 Task Force recommenda-
sity and prediabetes (12–14). tion statement. JAMA.
kcal/d and engage in 150 minutes of 2020;324:2069-2075.
The Diabetes Prevention Program, an moderate physical activity per week [PMID: 33231670]
12. Knowler WC, Barrett-
RCT of 3234 U.S. patients with predia- with a goal of achieving weight loss of Connor E, Fowler SE, et
al; Diabetes Prevention
betes (mean age, 51 years; mean BMI, 5% to 10% (15). If intensive lifestyle Program Research Group.
34 kg/m2), showed that an intensive life- changes cannot be implemented, clini- Reduction in the inci-
dence of type 2 diabetes
style modification program aimed at a cians may consider adding metformin. with lifestyle intervention
or metformin. N Engl J
Med. 2002;346:393-403.
[PMID: 11832527]
13. Knowler WC, Fowler SE,
Screening and Prevention... Screening for T2D in patients with risk factors may lead Hamman RF, et al. 10-
to earlier treatment and fewer complications. In patients with prediabetes, intensive life- year follow-up of diabetes
style programs aimed at weight loss that include reducing calories and increasing physi- incidence and weight loss
in the Diabetes
cal activity can prevent T2D; metformin may be considered. Prevention Program
Outcomes Study. Lancet.
2009;374:1677-1686.
[PMID: 19878986]
CLINICAL BOTTOM LINE 14. Lindström J, Louheranta
A, Mannelin M, et al;
Finnish Diabetes
Prevention Study Group.
The Finnish Diabetes
Prevention Study (DPS):

Diagnosis and Evaluation lifestyle intervention and

3-year results on diet and
physical activity. Diabetes
What are the diagnostic criteria for the U.S. Food and Drug Administration Care. 2003;26:3230-
3236. [PMID: 14633807]
T2D in nonpregnant adults? (FDA) can also be used. If patients have 15. Gilden AH, Catenacci VA,
In patients with unequivocal symptoms conditions that change the relationship Taormina JM. Obesity.
Ann Intern Med.
of hyperglycemia (polyuria, polydipsia, between HbA1c and glycemia (such as 2024;177:ITC65-ITC80.
16. Karter AJ, Parker MM,
weight loss), a single random plasma pregnancy, hemoglobinopathies, glu- Moffet HH, et al. Racial
and ethnic differences in
glucose level of 200 mg/dL (11.1 cose-6-phosphate dehydrogenase defi- the association between
mmol/L) or higher is diagnostic. Per the ciency, HIV, hemodialysis, or recent mean glucose and hemo-
globin A1c. Diabetes
ADA (5), diagnosis can also be based blood loss), only plasma blood glucose Technol Ther.
2023;25:697-704.
on 2 abnormal results from different should be used to diagnose T2D (5). In [PMID: 37535058]
tests on the same sample (for example, addition, for a given mean glucose value, 17. Kaur G, Lakshmi PVM,
Rastogi A, et al.
fasting plasma glucose and HbA1c) or Black patients may have HbA1c values Diagnostic accuracy of
tests for type 2 diabetes
from different tests or the same test on that are 0.33 percentage points higher and prediabetes: a sys-
different samples (for example, 2 than those in White patients, potentially tematic review and meta-
analysis. PLoS One.
HbA1c tests). Thresholds for diagnostic leading to premature T2D diagnoses 2020;15:e0242415.
[PMID: 33216783]
tests (Table 1) include fasting plasma and overtreatment (16). An HbA1c thre- 18. American Diabetes
Association Professional
glucose level of 126 mg/dL (7.0 mmol/L) shold of 6.5% or higher may also miss Practice Committee. 4.
or higher, HbA1c level of 6.5% or higher, some T2D cases; a lower threshold of Comprehensive medical
evaluation and
or an oral glucose tolerance test with a 2- 6.03% had the highest sensitivity in one assessment of
comorbidities: Standards
hour plasma glucose level of 200 mg/dL meta-analysis (17). Thus, if clinical suspi- of Care in Diabetes—
or higher. Point-of-care HbA1c assays cion is high but results are borderline, 2024. Diabetes Care.
2024;47:S52-S76. [PMID:
that are NGSP-certified and approved by another test should be used. 38078591]

Annals of Internal Medicine In the Clinic ITC3 © 2024 American College of Physicians

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 Table 1. Diagnostic Criteria for Type 2 Diabetes*

Random Plasma Blood Glucose Two Abnormal Test Results From the Same or Different Samples
19. Young-Hyman D, de Level With Unequivocal
Groot M, Hill-Briggs F, et Hyperglycemia Symptoms Hemoglobin A1c Level 8-Hour Fasting 2-Hour Plasma Glucose
al. Psychosocial care for Plasma Glucose Level During an Oral
people with diabetes: a Level Glucose Tolerance Test
position statement of the
American Diabetes ≥200 mg/dL (≥11.1 mmol/L) ≥6.5% (≥48 mmol/mol) ≥126 mg/dL ≥200 mg/dL
Association. Diabetes with classic symptoms (≥7.0 mmol/L) (≥11.1 mmol/L)
Care. 2016;39:2126-
2140. [PMID: 27879358]
20. Hill-Briggs F, Adler NE, * Data are from reference 2.
Berkowitz SA, et al. Social
determinants of health
and diabetes: a scientific What should initial evaluation of patients or older should be assessed for cogni-
review. Diabetes Care.
2020;44:258-279. [PMID: with newly diagnosed T2D include? tive impairment.
33139407]
21. American Diabetes The goal of initial evaluation of patients Initial laboratory tests should assess glu-
Association Professional with newly diagnosed T2D should be cose control (HbA1c level), fasting lipid
Practice Committee. 5.
Facilitating positive health to identify CVRFs and diabetic compli- profile, nephropathy (urinary microalbu-
behaviors and well-being
to improve health
cations that would guide management. min–creatinine ratio and serum creati-
outcomes: Standards of The ADA recommends a detailed his- nine), and liver aminotransferases (to
Care in Diabetes—2024.
Diabetes Care. 2024;47:
tory that assesses risk factors for and detect fatty liver disease). At diagnosis,
S77-S110. [PMID: poor control of T2D complications; patients should be referred to an optom-
38078584]
22. Lichtenstein AH, Appel LJ, reviews diet, body weight, physical ac- etrist or ophthalmologist for a dilated
Vadiveloo M, et al. 2021 tivity, sleep, family history of T2D, social eye examination and comprehensive
dietary guidance to
improve cardiovascular history, vaccine history, and fracture assessment to evaluate for retinopathy.
health: a scientific state- risk; and assesses for CVD, cerebrovas-
ment from the American
Heart Association. cular disease, neuropathy, peripheral The ADA also recommends evaluating
Circulation. 2021;144:
e472-e487. [PMID:
vascular disease, sleep apnea, bone for symptoms of comorbid distress,
34724806] health, erectile dysfunction, depres- depression, anxiety, and disordered
23. Mirabelli M, Chiefari E,
Arcidiacono B, et al.
sion, anxiety, and disordered eating eating (19). Social history should
Mediterranean diet (18). The physical examination should include assessment for food insecurity,
nutrients to turn the tide
against insulin resistance include assessment of BMI and BP and housing instability, financial barriers,
and related diseases. inspection for possible T2D complica- and social support (20), as social deter-
Nutrients. 2020;12:1066.
24. Wong MG, Perkovic V, tions via CV, neurologic, skin, and foot minants of health influence T2D out-
Chalmers J, et al;
ADVANCE-ON
examinations. Patients aged 65 years comes (20).
Collaborative Group.
Long-term benefits of in-
tensive glucose control for
preventing end-stage kid- Diagnosis and Evaluation... Diagnosis of T2D is based on classic symptoms and a ran-
ney disease: ADVANCE- dom blood glucose level of 200 mg/dL or higher, or 2 abnormal test results on the same
ON. Diabetes Care.
2016;39:694-700. [PMID:
or different samples. Initial evaluation includes a comprehensive history, physical examina-
27006512] tion, and laboratory testing to assess risk factors, comorbidities, and T2D complications.
25. Action to Control
Cardiovascular Risk in
Diabetes Follow-On Eye
Study Group. Persistent CLINICAL BOTTOM LINE
effects of intensive
glycemic control on
retinopathy in type 2
diabetes in the Action to
Control Cardiovascular
Risk in Diabetes
(ACCORD) Follow-On
Study. Diabetes Care.
2016;39:1089-1100.
Treatment
[PMID: 27289122] The goals of management are to decrease or obesity, the ADA recommends in-
26. Duckworth W, Abraira C,
Moritz T, et al; VADT risk for diabetes-related complications by tensive behavioral lifestyle interven-
Investigators. Glucose achieving normal glucose levels (especially tions that include diet and exercise
control and vascular com-
plications in veterans with in people who are newly diagnosed) while modifications (21) with a goal of achiev-
type 2 diabetes. N Engl J
Med. 2009;360:129-139. minimizing risk for hypoglycemia. ing at least a 5% weight loss.
[PMID: 19092145]
27. Reaven PD, Emanuele NV, What nonpharmacologic Various diets and eating patterns are
Wiitala WL, et al; VADT
Investigators. Intensive interventions are effective in glycemic recommended, including DASH (Die-
glucose control in patients
with type 2 diabetes—15- control for patients with T2D? tary Approaches to Stop Hyperten-
year follow-up. N Engl J
Med. 2019;380:2215-
Because weight loss improves glyce- sion), Mediterranean, high-fiber, low-fat,
2224. [PMID: 31167051] mic control in people with overweight vegetarian, vegan, and low-carbohydrate

© 2024 American College of Physicians ITC4 In the Clinic Annals of Internal Medicine

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diets. Whole-foods plant-based, DASH, What is the target HbA1c level?
and Mediterranean diets have been HbA1c is the main measure of glycemic 28. ACCORD Study Group.
Nine-year effects of 3.7
shown to confer cardioprotective ben- control, and the target level should be years of intensive
glycemic control on
efits (22). Although a range of cardio- individualized to the patient. Major cardiovascular outcomes.
protective eating patterns exist, they RCTs confirm that lowering HbA1c level Diabetes Care.
2016;39:701-708.
share many principles. Recommended decreases risk for microvascular com- [PMID: 26822326]
29. Gerstein HC, Miller ME,
diets emphasize nonstarchy vegeta- plications in patients with newly diag- Byington RP, et al; Action
bles, fruits, and whole grains as well as nosed (6, 7) and established (24, 25) to Control Cardiovascular
Risk in Diabetes Study
low-fat dairy products, minimal added diabetes, although the reduction in Group. Effects of intensive
glucose lowering in type
sugars, and minimally processed foods macrovascular complications appears 2 diabetes. N Engl J Med.

(Appendix Table 1, available at Annals. to take decades to accrue (8) and may 2008;358:2545-2559.
[PMID: 18539917]
org). The ADA recommends nutrient- not apply to patients with established 30. Patel A, MacMahon S,
Chalmers J, et al;
dense, high-fiber foods; carbohydrates diabetes (26–28). ADVANCE Collaborative
Group. Intensive blood glu-
from nonstarchy vegetables, fruits, and In the UKPDS (United Kingdom Pros- cose control and vascular
outcomes in patients with
whole grains; dairy products with mini- pective Diabetes Study), patients with type 2 diabetes. N Engl J
Med. 2008;358:2560-
mal added sugar (21); Mediterranean- newly diagnosed diabetes who were 2572. [PMID: 18539916]
style diets rich in monounsaturated and randomly assigned to intensive control 31. Zoungas S, Chalmers J,
Neal B, et al; ADVANCE-
polyunsaturated fats as well as foods (mean achieved HbA1c level of 7.0%) ON Collaborative Group.
Follow-up of blood-pres-
rich in omega-3 fatty acids, such as fatty had lower rates of early, asymptomatic sure lowering and glu-
fish, nuts, and seeds; and intake of microvascular outcomes (8.6 vs. 11.4 cose control in type 2
diabetes. N Engl J Med.
water instead of sugar-sweetened bev- per 1000 patient-years) but not clear 2014;371:1392-1406.
[PMID: 25234206]
erages (including fruit juices). These benefits for CV outcomes versus those 32. Qaseem A, Wilt TJ,

eating patterns have been associated in the control group (mean achieved Kansagara D, et al;
Clinical Guidelines
with improved insulin resistance (23). HbA1c level of 7.9%) (7). In a 20-year fol- Committee of the
American College of
low-up study, the group initially as- Physicians. Hemoglobin
A1c targets for glycemic
Patients with elevated BMI (≥25 kg/m2 signed to intensive control had lower control with pharmaco-
[≥23 kg/m2 for Asian persons]) should rates of myocardial infarction (MI) (16.8 logic therapy for nonpreg-
nant adults with type 2
be advised to reduce caloric intake by vs. 19.6 per 1000 patient-years) and diabetes mellitus: a guid-
ance statement update
500 to 1000 kcal/d by focusing on death (26.8 vs. 30.3 per 1000 patient- from the American

foods with low caloric density, such as years), even though differences in gly- College of Physicians.
Ann Intern Med.
lean protein, fruits, and nonstarchy veg- cemic control were not maintained 2018;168:569-576.
[PMID: 29507945]
between groups (8).
etables, as well as limited added sugar 33. American Diabetes
Association Professional
and refined carbohydrates. Many struc- Subsequent trials in patients with Practice Committee. 9.
Pharmacologic
tured diets that allow lower caloric established diabetes affirmed benefits approaches to glycemic
treatment: Standards of
intake have been shown to improve of glycemic control for microvascular Care in Diabetes—2024.
weight loss; thus, counseling should complications (24, 25) but not for mac- Diabetes Care. 2024;47:
S158-S178. [PMID:
focus on strategies that individual rovascular outcomes (26–28); 1 trial 38078590]
34. Zinman B, Wanner C,
patients can adhere to. Additional in- showed increased risk for death (29). Lachin JM, et al; EMPA-REG
OUTCOME Investigators.
formation about effective eating plans In ADVANCE (Action in Diabetes and Empagliflozin, cardiovascu-
to produce weight loss are available in Vascular Disease: Preterax and Diamicron-
lar outcomes, and mortality
in type 2 diabetes. N Engl J
the In the Clinic on obesity (15). MR Controlled Evaluation), 11 140 pa- Med. 2015;373:2117-
2128. [PMID: 26378978]
tients with T2D (mean age, 66 years; 35. Wanner C, Inzucchi SE,
The ADA recommends at least 150 mean T2D duration, 8 years; 32% with
Lachin JM, et al; EMPA-
REG OUTCOME
minutes of moderate- to vigorous-in- prior CV event) who were randomly as- Investigators.
Empagliflozin and pro-
tensity aerobic physical activity per signed to intensive control (mean HbA1c gression of kidney disease
in type 2 diabetes. N Engl
week and at least 2 days of resistance level of 6.5% vs. 7.3% in the control group) J Med. 2016;375:323-
training per week, which have been (30) had reduced nephropathy (4.1% 334. [PMID: 27299675]
36. Perkovic V, Jardine MJ,
shown to reduce HbA1c level, decrease vs. 5.2%; P ¼ 0.006) but no change in Neal B, et al; CREDENCE
Trial Investigators.
weight, and improve CVRFs (21). CV events or mortality after a median of Canagliflozin and renal
outcomes in type 2 diabe-
Ideally, aerobic physical activity and re- 5 years. In posttrial follow-up, the inten- tes and nephropathy. N
sistance training should be distributed sive control group had lower rates of Engl J Med.
2019;380:2295-2306.
across the week. end-stage renal disease but no change [PMID: 30990260]

Annals of Internal Medicine In the Clinic ITC5 © 2024 American College of Physicians

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37. Wiviott SD, Raz I, Bonaca in CV events or all-cause mortality (24, Physicians (ACP) recommended that
MP, et al; DECLARE–TIMI
58 Investigators. 31). most people with T2D have an HbA1c
Dapagliflozin and cardio-
vascular outcomes in type level of 7% to 8%, as lower targets were
In the VADT (Veterans Affairs Diabetes
2 diabetes. N Engl J Med. not found to reduce mortality or macro-
2019;380:347-357. Trial) of 1791 older veterans with long- vascular benefit but did result in signifi-
[PMID: 30415602]
38. Marso SP, Bain SC, standing diabetes (mean diabetes du- cant harms in addition to hypoglycemia.
Consoli A, et al; SUSTAIN-
6 Investigators. ration, 11.5 years; 40% with a prior CV However, for those with a life expectancy
Semaglutide and cardio- event) (26), intensive control did not longer than 15 years, ACP acknowl-
vascular outcomes in
patients with type 2 dia- have a greater effect on the primary edged that a lower target may be rea-
betes. N Engl J Med.
2016;375:1834-1844. composite outcome (CV events, heart sonable (32).
[PMID: 27633186]
39. Marso SP, Daniels GH,
failure, vascular surgery, and amputa-
Brown-Frandsen K, et al; tion; mortality; or microvascular events) When should treatment include
LEADER Trial Investigators.
Liraglutide and cardiovas- despite achieving greater HbA1c reduc- pharmacotherapy?
cular outcomes in type 2 tion (mean, 6.9% vs. 8.4%) after a me- Once an HbA1c goal has been estab-
diabetes. N Engl J Med.
2016;375:311-322. dian of 5.6 years. However, there was a lished, pharmacologic management
[PMID: 27295427]
40. Gerstein HC, Colhoun reduction in albuminuria (26). After 15 should be instituted if lifestyle changes
HM, Dagenais GR, et al;
years of follow-up, mortality (hazard ra- alone do not achieve the goal within
REWIND Investigators.
Dulaglutide and cardio- tio [HR], 1.02 [CI, 0.88 to 1.18]) and approximately 6 to 8 weeks. Patients
vascular outcomes in type
2 diabetes (REWIND): a CVD risk (HR, 0.91 [CI, 0.78 to 1.06]) did with severe hyperglycemia (random
double-blind, randomised
not differ between groups (27). blood glucose level consistently ≥180
placebo-controlled trial.
Lancet. 2019;394:121- mg/dL [≥10.0 mmol/L]) or symptoms
130. [PMID: 31189511] ACCORD (Action to Control Cardio- (polydipsia, polyuria, weight loss) require
41. Gerstein HC, Colhoun
HM, Dagenais GR, et al; vascular Risk in Diabetes), an RCT of immediate pharmacologic intervention.
REWIND Investigators.
Dulaglutide and renal out-
10 251 U.S. patients with T2D (mean age,
comes in type 2 diabetes: 62.2 years; median T2D duration, 10 How should physicians select
an exploratory analysis of noninsulin glucose-lowering
the REWIND randomised, years; 35% with a prior CV event) (29),
placebo-controlled trial.
was stopped early because of a 22% pharmacotherapies?
Lancet. 2019;394:131-
138. [PMID: 31189509] increase in mortality in the intensive There are many noninsulin pharmaco-
42. Michos ED, Lopez-
Jimenez F, Gulati M. Role control group (5.0% vs. 4.0%; P ¼ 0.04). logic options, making selection of a
of glucagon-like peptide-1
The primary end point (nonfatal MI, glucose-lowering medication challeng-
receptor agonists in
achieving weight loss and nonfatal stroke, and CV death) did not ing. Selection should consider the
improving cardiovascular
outcomes in people with differ between groups. Long-term fol- patient's level of glycemic control; the
overweight and obesity. J
low-up suggested an ongoing greater agent's efficacy in achieving glycemic
Am Heart Assoc. 2023;12:
e029282. [PMID: risk for CV events (28) but lower rates of control and its other therapeutic bene-
37278394]
43. Qaseem A, Obley AJ, retinopathy with intensive control (25). fits; the patient's risk for atherosclerotic
Shamliyan T, et al; Clinical cardiovascular disease (ASCVD), heart
Guidelines Committee of
the American College of Given the overall evidence, the target failure, renal protection, and obesity;
Physicians. Newer phar-
macologic treatments in
HbA1c level should be individualized drug costs; and the patient's preferences.
adults with type 2 diabe- depending on duration of T2D, prior
tes: a clinical guideline
diabetic complications, age, life ex- Table 2 provides an overview of the
from the American
College of Physicians. Ann pectancy, risk for hypoglycemia, overall major classes of noninsulin agents
Intern Med. 19 April
2024. [Epub ahead of health, and patient preferences. The available to treat T2D, their relative effi-
print].
ADA recommends an HbA1c target of cacy, and clinical considerations based
44. Aroda VR, Edelstein SL,
Goldberg RB, et al;
less than 7.0% for many nonpregnant on the 2024 ADA guidelines (33).
Diabetes Prevention
Program Research Group. adults if it is achievable without signifi- Biguanides, sodium–glucose cotrans-
Long-term metformin use porter-2 inhibitors (SGLT2-Is), and glu-
and vitamin B12 defi- cant hypoglycemia (5); lower HbA1c
ciency in the Diabetes cagon-like peptide-1 receptor agonists
Prevention Program
goals may be reasonable based on
(GLP-1RAs) are most often considered
Outcomes Study. J Clin patient preference and clinician judg-
Endocrinol Metab. first-line treatment depending on
2016;101:1754-1761. ment if they are achievable without sig-
[PMID: 26900641] patients' underlying ASCVD risk and
45. Frías JP, Davies MJ, nificant hypoglycemia, and higher HbA1c
comorbidities.
Rosenstock J, et al; targets may be reasonable when harms
SURPASS-2 Investigators.
Tirzepatide versus sema- of treatment outweigh potential benefits Biguanides, such as metformin, de-
glutide once weekly in
patients with type 2 dia- and for patients with short life expect- crease gluconeogenesis in the liver,
betes. N Engl J Med.
2021;385:503-515.
ancy. In contrast, in its 2017 guidance thereby reducing blood glucose.
[PMID: 34170647] statement, the American College of SGLT2-Is (dapagliflozin, empagliflozin)

© 2024 American College of Physicians ITC6 In the Clinic Annals of Internal Medicine

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Table 2. Major Noninsulin Medications Available in the United States for Type 2 Diabetes*

Drug Class Indication Name HbA1c Efficacy Weight Loss Other Benefits Initial Dose Maximum Usual Dose Considerations
Dose

Biguanides† Patients without Metformin High Neutral — 500 mg twice 2550 mg/d 500–1000 mg GI tolerance may be
ASCVD, HF, daily or 850 twice daily improved with
CKD, high risk mg/d slow titration or
for ASCVD, or using extended-
Metformin 500 mg/d 2000 mg/d 1500–2000
overweight or release; monitor
extended- mg/d
obesity based for vitamin B
release
on BMI deficiency
SGLT2-Is† Patients with Canagliflozin Intermediate Intermediate ;CV death, nonfatal 100 mg/d 300 mg/d 100–300 mg/d Increased risk for
ASCVD, HF, or high MI, nonfatal stroke genital mycotic
CKD, high risk ;HF hospitalization infections (rare
for ASCVD, or ;End-stage renal reports of peri-
overweight or disease neum necrotizing
obesity based fasciitis); affects
Empagliflozin ;CV death 10 mg/d 25 mg/d 10–25 mg/d
on BMI‡ volume status
;HF hospitalization
;Death
;End-stage renal
disease
Dapagliflozin ;CV death 5 mg/d 10 mg/d 5–10 mg/d
;HF hospitalization
Ertugliflozin — 5 mg/d 15 mg/d 5–15 mg/d
GLP-1RAs†§ Patients with Semaglutide High or very Very high ;CV death, nonfatal 0.25 mg/wk 1 mg/wk 0.5 mg/wk All injectable, and
ASCVD, HF, high MI, nonfatal stroke semaglutide also
CKD, high risk ;Nephropathy available as oral;
for ASCVD, or :risk for thyroid
Dulaglutide High ;CV death, nonfatal 0.75 mg/wk 1.5 mg/wk 0.75–1.5 mg/wk
overweight or c-cell tumors in
MI, nonfatal stroke
obesity based rodents; possible
;Nephropathy
on BMI‡ :risk for pancreati-
Liraglutide High ;CV death, nonfatal 0.6 mg/d 1.8 mg/d 1.2 mg/d tis, gallbladder
MI, nonfatal stroke disease; GI toler-
Exenatide Intermediate — 5 mcg twice 10 mcg twice 5–10 mcg/d ance may improve
daily (≤60 min daily with dietary
before meals) modifications

Exenatide Intermediate — 2 mg once per 2 mg once 2 mg once per

extended- week per week week
release
Lixisenatide Intermediate — 10 mcg/d 20 mcg/d 20 mcg/d
GLP-1/GIP receptor Patients with Tirzepatide Very high Very high — 2.5 mg weekly 15 mg/wk — Same as GLP-1RAs
agonist†§ overweight or for 4 wk, then
(injection) obesity based 5 mg weekly;
on BMI and increase by
without 2.5 mg/wk
ASCVD, HF, every 4 wk
CKD, or high
risk for ASCVD
DPP-4Is§ — Sitagliptin Intermediate Neutral — 100 mg/d 100 mg/d 100 mg/d Possible :risk for
pancreatitis, joint
Saxagliptin 2.5 mg/d 5 mg/d 5 mg/d
pain, bullous pem-
Linagliptin 5 mg/d 5 mg/d 5 mg/d phigoid; evaluate
Alogliptin 25 mg/d 25 mg/d 25 mg/d for gallbladder
disease
Thiazolidinediones — Pioglitazone High Neutral to mild — 15–30 mg/d 45 mg/d 15–45 mg/d :risk for heart fail-
weight gain ure, fluid reten-
Rosiglitazone 4 mg/d (or 8 mg/d 4–8 mg/d (or
tion, fracture;
twice daily) twice daily)
benefits in nonal-
coholic fatty liver
disease
Sulfonylureas — Glimepiride High Mild weight — 1–2 mg/d 8 mg/d 4 mg/d Increases
(second gener- gain hypoglycemia
Glipizide 2.5–5 mg/d 40 mg/d 10–20 mg/d (or
ation)
twice daily)
Glipizide sus- 5 mg/d 20 mg/d 5–20 mg/d (or
tained-release twice daily)
Glyburide† 2.5–5 mg/d 20 mg/d 5–20 mg/d (or
twice daily)
Glyburide 0.75–3 mg/d 12 mg/d 3–12 mg/d (or
micronized† twice daily)

ASCVD ¼ atherosclerotic cardiovascular disease; BMI ¼ body mass index; CKD ¼ chronic kidney disease; CV ¼ cardiovascular; DPP-4I ¼
dipeptidyl peptidase-4 inhibitor; GI ¼ gastrointestinal; GIP ¼ glucose-dependent insulinotropic polypeptide; GLP-1RA ¼ glucagon-like
peptide-1 receptor agonist; HbA1c ¼ hemoglobin A1c; HF ¼ heart failure; MI ¼ myocardial infarction; SGLT2-I ¼ sodium–glucose
cotransporter-2 inhibitor.
* Data are from reference 33.
† Not recommended in pregnant persons.
‡ Effects of GLP-1RAs and SGLT2-Is in patients with ASCVD, HF, and CKD and at high risk for ASCVD differ within each class. See
“Other Benefits” for details.
§ GLP-1RAs and DPP-4Is should not be combined.

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 reduce reabsorption of renally filtered events in RCTs (38–40), but only dula-
glucose, which promotes renal excre- glutide and semaglutide reduced ne-
46. Aroda VR, Rosenstock J,
Terauchi Y, et al; PIONEER tion of glucose. GLP-1RAs (linagliptin, lir- phropathy (38, 41).
1 Investigators. PIONEER aglutide, semaglutide), GLP-1/glucose-
1: randomized clinical In an RCT of once-weekly semaglutide
trial of the efficacy and dependent insulinotropic polypeptide
safety of oral semaglutide versus placebo among 3297 patients
monotherapy in compari- (GIP) receptor agonists (tirzepatide), and
with T2D and high CV risk (83.0% with
son with placebo in dipeptidyl peptidase-4 inhibitors (DPP-
patients with type 2 dia- prior CV or chronic kidney disease
betes. Diabetes Care. 4Is) (alogliptin, linagliptin, saxagliptin,
2019;42:1724-1732. [CKD]), patients who received semaglu-
[PMID: 31186300] sitagliptin) all work through mechanisms
47. Pratley R, Amod A, Hoff tide had lower risk for the composite
that promote insulin release, which en-
ST, et al; PIONEER 4 inves- CV end point of the first occurrence of
tigators. Oral semaglutide hances insulin sensitivity, and also de-
versus subcutaneous lira- CV death, nonfatal MI, or nonfatal
glutide and placebo in crease glucagon. GLP-1RAs differ from
type 2 diabetes (PIONEER stroke (6.6% vs. 8.9%; HR, 0.74 [CI, 0.58
DPP-4Is in also increasing satiety and
4): a randomised, double- to 0.95]) but not lower mortality (38).
blind, phase 3a trial. slowing gastric emptying. Thiazolidi-
Lancet. 2019;394:39-50. Semaglutide also reduced incident ne-
[PMID: 31186120] nediones work by increasing insulin sensi-
48. Del Prato S, Kahn SE, phropathy (3.8% vs. 6.1%; HR, 0.64 [CI,
Pavo I, et al; SURPASS-4
tivity and glucose utilization. Sulfonylureas
0.46 to 0.88]) but resulted in higher
Investigators. Tirzepatide work by stimulating pancreatic b cells to
versus insulin glargine in rates of worsening retinopathy requir-
type 2 diabetes and secrete insulin.
increased cardiovascular ing treatment (3.0% vs. 1.8%; HR, 1.76
risk (SURPASS-4): a rando-
mised, open-label, paral-
In patients with or at high risk for ASCVD [CI, 1.11 to 2.78]).
lel-group, multicentre, (such as those aged ≥55 years with 2
phase 3 trial. Lancet. The reductions in CV outcomes associ-
2021;398:1811-1824. CVRFs), strong evidence suggests and
[PMID: 34672967] ated with SGLT2-Is and GLP-1RAs have
49. Home PD, Pocock SJ, the 2024 ADA guideline recommends
primarily been shown in patients with
Beck-Nielsen H, et al; that GLP-1RAs and/or SGLT2-Is are the
RECORD Study Team. preexisting CVD or high ASCVD risk
Rosiglitazone evaluated preferred initial choice depending on
for cardiovascular out- and may not be generalizable to
comes in oral agent com- the underlying comorbidity (33).
bination therapy for type
patients with lower baseline risk.
2 diabetes (RECORD): a The EMPA-REG trial (n ¼ 7020) found
multicentre, randomised, The DECLARE–TIMI 58 (Dapagliflozin
open-label trial. Lancet. that patients with T2D and high CV risk
2009;373:2125-2135. Effect on Cardiovascular Events–
[PMID: 19501900] randomly assigned to the SGLT2-I
Thrombolysis in Myocardial Infarction
50. American Diabetes empagliflozin had a reduction in a com-
Association Professional 58) trial, which randomly assigned
Practice Committee. 15. posite CV outcome (death from CV
Management of diabetes 17 160 patients with T2D (10 186 with-
in pregnancy: Standards causes, nonfatal MI, or nonfatal stroke)
out baseline CV disease), found no
of Care in Diabetes—2024. (10.5% vs. 12.1% in the placebo group;
Diabetes Care. 2024;47: difference in the primary composite
S282-S294. [PMID: HR, 0.86 [CI, 0.74 to 0.99]) (34). The
38078583] outcome of CV death, MI, or stroke
51. Muller DRP, Stenvers DJ, empagliflozin group also had lower all-
Malekzadeh A, et al.
but found a reduction in hospitaliza-
cause mortality (5.7% vs. 8.3%; HR, 0.68
Effects of GLP-1 agonists tion for heart failure (HR, 0.73 [CI, 0.61
and SGLT2 inhibitors dur- [CI, 0.57 to 0.82]), driven largely by a dif-
ing pregnancy and lacta- to 0.88]) and renal end points (HR,
tion on offspring ference in CV mortality, and had better
outcomes: a systematic 0.76 [CI, 0.67 to 0.87]) with dapagliflo-
renal outcomes (lower rates of doubling
review of the evidence. zin compared with placebo (37).
Front Endocrinol of serum creatinine level and initiation of
(Lausanne).
2023;14:1215356. renal replacement therapy) (35). RCTs also demonstrate that GLP-1RAs
[PMID: 37881498]
52. Martens T, Beck RW,
such as liraglutide and semaglutide pro-
Subsequent clinical trials suggest that
Bailey R, et al; MOBILE duce clinically important weight loss
Study Group. Effect of con- the ASCVD benefits associated with
tinuous glucose monitor- and are FDA-approved for treatment of
ing on glycemic control in SGLT2-Is and GLP-1RAs seem to be
patients with type 2 dia- obesity; thus, these drugs might be a
class effects; however, other benefits
betes treated with basal reasonable first choice for patients with
insulin: a randomized are medication-specific. For example,
clinical trial. JAMA. obesity and related CVD comorbidities
2021;325:2262-2272. among SGLT2-Is, RCTs show that cana-
[PMID: 34077499] according to the ADA (42).
53. Bao S, Bailey R, Calhoun gliflozin, dapagliflozin, and empagliflo-
P, et al. Effectiveness of zin improve CV outcomes (34, 36, 37), In patients without ASCVD risk or the
continuous glucose moni-
toring in older adults with but only canagliflozin and empagliflozin aforementioned indications for SGLT2-
type 2 diabetes treated
with basal insulin. also improved renal outcomes (35, 36). Is or GLP-1RAs, metformin is recom-
Diabetes Technol Ther.
2022;24:299-306. [PMID:
Similarly, the GLP-1RAs dulaglutide, lira- mended as first-line therapy and a
34939824] glutide, and semaglutide reduced CV lower-cost alternative (33, 43). Although

© 2024 American College of Physicians ITC8 In the Clinic Annals of Internal Medicine

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metformin is not as efficacious as GLP- heart failure or GLP-1RAs to reduce risk
1RAs in promoting weight loss, the for all-cause mortality, major adverse car-
UKPDS trial showed that in patients diovascular events, and stroke. In its
whose body weight was 20% higher updated 2024 guideline, ACP also rec-
than ideal, metformin was superior to ommended against using DPP-4Is for
sulfonylureas and insulin in reducing treatment of T2D (43).
mortality despite identical levels of gly- 54. Beck RW, Riddlesworth

cemic control (6). Metformin should not The newer dual-acting GLP-1/GIP re- TD, Ruedy K, et al;
DIAMOND Study Group.
be used in persons with severe renal ceptor agonist tirzepatide was superior Continuous glucose moni-
toring versus usual care
insufficiency (glomerular filtration rate in reducing HbA1c compared with a 1- in patients with type 2 di-

[GFR] <30 mL/min/1.73 m2), acute de- mg dose of semaglutide (2 to 2.3 abetes receiving multiple
daily insulin injections: a

compensated heart failure, or severe vs. 1.86 percentage points) (45) and randomized trial. Ann
Intern Med.
liver disease because of its drug metab- insulin glargine (2.43 and 2.58 vs. 2017;167:365-374.
[PMID: 28828487]
olism. Patients taking metformin for 1.44 percentage points) (48) in RCTs, 55. American Diabetes

more than 4 years should be screened so this drug may be preferred in Association Professional
Practice Committee. 7.
patients who need large improvements Diabetes technology:
for vitamin B12 deficiency because met-
in their HbA1c and are trying to avoid Standards of Care in
formin reduces vitamin B12 levels (44). Diabetes—2024. Diabetes
insulin; however, no studies have Care. 2024;47:S126-
The periodicity of screening is unknown, directly compared tirzepatide with a 2- S144. [PMID: 38078575]
56. Isitt JJ, Roze S, Sharland
although the ADA recommends annual mg dose of semaglutide. H, et al. Cost-effectiveness
screening. of a real-time continuous
glucose monitoring sys-
Other noninsulin options, including sul- tem versus self-monitor-
If metformin is contraindicated or not fonylureas, thiazolidinediones, and ing of blood glucose in
people with type 2 diabe-
tolerated, the next choice of agent a-glucosidase inhibitors, are not pre- tes on insulin therapy in
the UK. Diabetes Ther.
should be dictated by patient factors, ferred because of their adverse effect 2022;13:1875-1890.
including BMI, preferences for method profiles. Sulfonylureas can cause hypo- [PMID: 36258158]
57. Patel MS, Patel SB,
of delivery (oral vs. injectable), adverse glycemia and weight gain and are Steinberg MB. Smoking
cessation. Ann Intern
effects, and cost. As described previ- unlikely to provide CV benefits beyond Med. 2021;174:ITC177-
ously, SGLT2-Is may provide greater glucose control. Thiazolidinediones ITC192. [PMID:
34904907]
benefit in CV and renal outcomes. In can increase risk for heart failure and 58. American Diabetes
addition, for patients with overweight fracture, although they probably do Association Professional
Practice Committee. 10.
or obesity, GLP-1RAs and dual-acting not increase total CV events (49). Short- Cardiovascular disease

GLP-1/GIP receptor agonists may be acting agents, such as a-glucosidase and risk management:
Standards of Care in
reasonable options because of their inhibitors (acarbose, miglitol) and non- Diabetes—2024. Diabetes
Care. 2024;47:S179-
weight loss benefits. One RCT showed sulfonylurea insulin secretagogues (nate- S218. [PMID: 38078592]

that subcutaneous semaglutide and tir- glinide, repaglinide), improve postpran- 59. Qaseem A, Wilt TJ, Rich
R, et al; Clinical
dial hyperglycemia and may be useful in Guidelines Committee of
zepatide led to significant weight loss the American College of
persons with inconsistent mealtimes.
(5.7 and 7.6 to 11.2 kg, respec- Physicians and the
Commission on Health of
tively) (45). The GLP-1RA semaglutide Most patients with T2D have worsening the Public and Science of
the American Academy of
also comes in oral form, which has also glycemic control over time. Increasing Family Physicians.
been shown to improve glycemic con- Pharmacologic treatment
the dose of existing agents is generally of hypertension in adults
trol and weight (46) and was noninfe- the first step to maintain control, but aged 60 years or older to
higher versus lower blood
rior to subcutaneous liraglutide for response may be limited. Patients often pressure targets: a clinical
weight loss (47). DPP-4Is are a reasona- require additional agents. Several com- practice guideline from
the American College of
ble choice for patients who prefer oral bination formulations of oral agents are Physicians and the
American Academy of
agents, are unable to receive oral sem- available and may provide advantages Family Physicians. Ann
aglutide due to insurance, and cannot in convenience or cost. Intern Med.
2017;166:430-437.
take a GLP-1RA. ACP recommends met- For women who are interested in
[PMID: 28135725]
60. Chen R, Suchard MA,
formin and lifestyle changes for all peo- becoming pregnant or are already Krumholz HM, et al.
Comparative first-line
ple with T2D; in those with inadequate pregnant, preconception counseling is effectiveness and safety of
glycemic control, ACP recommends recommended with referral to an endo- ACE (angiotensin-convert-
ing enzyme) inhibitors
adding SGLT2-Is to reduce risk for all- crinologist to manage medications. and angiotensin receptor
blockers: a multinational
cause mortality, major adverse cardio- Several medications, including metfor- cohort study.
vascular events, progression of CKD, min, glyburide, GLP-1RAs, and SGLT2- Hypertension.
2021;78:591-603.
and hospitalization due to congestive Is, are not recommended because they [PMID: 34304580]

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 cross the placenta (50, 51). Insulin ther- insulin may be considered, usually
apy is considered first-line treatment starting with a dose before the largest
61. Canoy D, Copland E,
Nazarzadeh M, et al;
(50). meal of the day. For those needing
Blood Pressure Lowering
When should physicians consider high doses of insulin, higher concentra-
Treatment Trialists
Collaboration.
insulin therapy? tions of insulin are available, including
Antihypertensive drug
effects on long-term blood Insulin therapy may be necessary for U-200, U-300, and U-500 formulations.
pressure: an individual-
level data meta-analysis patients who have severe hyperglyce- What is the role of home glucose
of randomised clinical tri-
als. Heart. mia (weight loss, polyuria, polydipsia) monitoring?
2022;108:1281-1289.
[PMID: 35058294]
and to achieve glycemic control (usu- Home glucose monitoring in the form
62. Weir MR. In the clinic: ally in combination with noninsulin of standard blood glucose meters or
hypertension. Ann Intern
Med. 2014;161:ITC1- therapy). Insulin is also first-line therapy continuous glucose monitors (CGMs)
ITC16. [PMID: 25437425] for women who are interested in be-
63. Heart Protection Study should be recommended when pa-
Collaborative Group. coming or are already pregnant. Except tients are prescribed insulin therapy,
MRC/BHF Heart
Protection Study of for women who are or are planning to with advice to check glucose levels
cholesterol lowering with
simvastatin in 20,536
become pregnant, most patients with with each insulin injection per the ADA
high-risk individuals: a severe hyperglycemia should be started (52). It is considered standard of care
randomised placebo-
controlled trial. Lancet. on a GLP-1–based therapy before start- for persons receiving insulin therapy to
2002;360:7-22. [PMID:
12114036]
ing insulin (33). Fixed-dose combina- allow sensible dose adjustments, par-
64. Colantonio LD, Rosenson tions, such as basal insulin and GLP- ticularly with shorter-acting prepara-
RS, Deng L, et al.
Adherence to statin ther- 1RAs, are also available. tions. For some people not taking
apy among US adults insulin, home glucose monitoring may
between 2007 and 2014.
J Am Heart Assoc.
The many available insulin formulations help them make behavioral lifestyle
2019;8:e010376. [PMID: differ in their onset of action and dura- changes; however, evidence for imp-
30616455]
65. Arvanitis M, Lowenstein tion (Appendix Table 2, available at roving glycemic control in people who
CJ. Dyslipidemia. Ann
Intern Med. 2023;176:
Annals.org). No particular regimen is are not receiving insulin therapy is lim-
ITC81-ITC96. [PMID: clearly superior, as most patients have ited. Home glucose monitoring allows
37307585]
66. Bowman L, Mafham M, a 1% to 2% decrease in HbA1c level af- patients and clinicians to assess glu-
Wallendszus K, et al;
ASCEND Study
ter starting therapy. Patients receiving cose control longitudinally, can provide
Collaborative Group. insulin therapy are at high risk for hypo- real-time feedback on the effects of dia-
Effects of aspirin for pri-
mary prevention in per- glycemia and often gain weight. There- betes self-management and treatments,
sons with diabetes fore, patients receiving insulin should be and should be used if symptoms of
mellitus. N Engl J Med.
2018;379:1529-1539. prescribed home glucose monitoring hyperglycemia or hypoglycemia are
[PMID: 30146931]
67. Davidson KW, Barry MJ, and should be educated about recogniz- present.
Mangione CM, et al; US
Preventive Services Task
ing and self-managing hypoglycemia. Patients using standard blood glucose
Force. Aspirin use to pre-
vent cardiovascular dis- Initially, most patients can be treated meters are generally advised to mea-
ease: US Preventive
with a single bedtime dose of neutral sure fasting glucose once daily if using
Services Task Force recom-
mendation statement. protamine Hagedorn (NPH) or basal long-acting insulin. After they achieve
JAMA. 2022;327:1577- normal fasting levels, preprandial and
1584. [PMID: 35471505] analogue insulin combined with metfor-
68. Hansson L, Lindholm LH,
min and a GLP-1RA. A basal analogue postprandial measurement may be
Niskanen L, et al. Effect of
helpful if HbA1c levels remain elevated.
angiotensin-converting-
enzyme inhibition com-
may be the first choice, although they
pared with conventional are considerably more expensive than Medicare expanded CGM coverage to
therapy on cardiovascular
morbidity and mortality in NPH insulin. Evidence suggests lower people with diabetes who take any
hypertension: the
Captopril Prevention
rates of hypoglycemia with basal ana- type of insulin and those who do not
Project (CAPPP) rando- logues, particularly newer, long-acting take insulin but have a history of hypo-
mised trial. Lancet.
1999;353:611-616. analogues, such as degludec. Typical glycemia. RCT data suggest that HbA1c
[PMID: 10030325] starting doses of insulin are 0.1 to 0.2 improves with CGM use in patients
69. Parving HH, Lehnert H,
Bröchner-Mortensen J, et units per kilogram of body weight. with T2D taking basal insulin (52), older
al; Irbesartan in Patients
with Type 2 Diabetes and
adults taking basal insulin (53), and
Microalbuminuria Study Some patients need twice-daily insulin patients with multiple insulin injections
Group. The effect of irbe- to achieve glycemic targets, and more (54). Continuous blood glucose moni-
sartan on the develop-
ment of diabetic frequent injections (such as preprandial tors are recommended especially for
nephropathy in patients
with type 2 diabetes. N injections) may be necessary for others. patients receiving multiple daily injec-
Engl J Med.
2001;345:870-878.
If HbA1c levels remain elevated despite tions and those who require continu-
[PMID: 11565519] normal fasting glucose levels, prandial ous insulin infusions and are not able

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to monitor with other devices (55). hypertension is available in the In the
Cost-effectiveness studies have found Clinic on hypertension (62).
that CGMs are likely to be cost-effective
compared with standard blood glu- ADA guidelines suggest using a risk-
cose meters (56). based approach to select patients for
lipid-lowering therapy for primary pre-
What other clinical interventions
vention (58). Patients with T2D who are
reduce and manage diabetes-related older than 40 years are likely to benefit
complications? from and should be treated with at
Besides glycemic control, optimal care least moderate-intensity statin therapy, 70. Bakris GL, Agarwal R,
of patients with T2D includes clinical regardless of their initial low-density Anker SD, et al; FIDELIO-
DKD Investigators. Effect
interventions to reduce CV and/or lipoprotein cholesterol (LDL-C) level of finerenone on chronic
kidney disease outcomes
ASCVD risk, screening for and manage- (63). High-intensity statin therapy is rec- in type 2 diabetes. N Engl
ment of other diabetes-related compli- ommended in patients with multiple J Med. 2020;383:2219-
2229. [PMID: 33264825]
cations and comorbidities, including ASCVD risk factors or a history of 71. Barry MJ, Nicholson WK,
nephropathy, retinopathy, and neurop- ASCVD. The ADA recommends a tar- Silverstein M, et al; US
Preventive Services Task
athy; and treatment of mental health get LDL-C reduction of at least 50% Force. Screening for
depression and suicide
conditions (Table 3). from baseline and a target LDL-C level risk in adults: US
below 70 mg/dL (1.8 mmol/L) for pri- Preventive Services Task
Force recommendation
CV risk reduction mary prevention and below 55 mg/dL statement. JAMA.

CV risk reduction includes smoking (1.4 mmol/L) for secondary prevention 2023;329:2057-2067.
[PMID: 37338872]
cessation, hypertension control, use of with statin treatment and, if necessary, 72. Katon WJ, Lin EH, Von
Korff M, et al.
lipid-lowering agents, aspirin use for ezetimibe or a proprotein convertase Collaborative care for
secondary prevention, and weight subtilisin/kexin type 9 (PCSK9) inhibitor patients with depression
and chronic illnesses. N
management (Table 3). Evidence- (58). For people with T2D aged 20 to Engl J Med.

based strategies to manage tobacco 39 years, statin therapy may be reason- 2010;363:2611-2620.
[PMID: 21190455]
dependence are reviewed in the In the able if they have additional ASCVD risk 73. McCarron RM, Shapiro B,
Rawles J, et al.
Clinic on smoking cessation (57). factors (58). In 2024, the ADA updated Depression. Ann Intern
its recommendations to include treat- Med. 2021;174:ITC65-
ITC80. [PMID: 33971098]
Hypertension is a major risk factor for ment with bempedoic acid or a PCSK9 74. Li R, Shrestha SS, Lipman

diabetes complications. Current guide- inhibitor in people who cannot tolerate R, et al; Centers for
Disease Control and
lines from the ADA, the American Co- statins (58). Long-term adherence to Prevention (CDC).
Diabetes self-manage-
llege of Cardiology, and the American statin therapy is low (64), so annual ment education and train-
Heart Association suggest a BP target measurement may be helpful to imp- ing among privately
insured persons with
of less than 130/80 mm Hg for patients rove adherence in those receiving ther- newly diagnosed diabetes
apy. For patients with T2D who are —United States, 2011–
with T2D (58). ACP recommends a sys- 2012. MMWR Morb
tolic BP target of less than 140 mm Hg younger than 40 years, measurement Mortal Wkly Rep.
2014;63:1045-1049.
for adults aged 60 years or older with of cholesterol is recommended at least [PMID: 25412060]
T2D (59). In addition to lifestyle chan- every 5 years to assess risk (58). De- 75. American Diabetes
Association Professional
ges, several drug classes are effective tailed information on cholesterol man- Practice Committee. 8.

for BP control, including angiotensin agement is reviewed in the In the Clinic Obesity and weight
management for the
receptor blockers (ARBs), angiotensin- on dyslipidemia (65). prevention and treatment
of type 2 diabetes:
converting enzyme inhibitors (ACEIs), Standards of Care in
dihydropyridine calcium-channel bloc- Patients with T2D and overweight or Diabetes—2024. Diabetes
Care. 2024;47:S145-
kers, and thiazide diuretics. ARBs and obesity should be evaluated and trea- S157. [PMID: 38078578]
ted. Intensive lifestyle modification is 76. Riddle MC, Cefalu WT,
ACEIs are often the initial agent be- Evans PH, et al.
the cornerstone for weight manage- Consensus report: defini-
cause of their beneficial renal effects,
ment; however, if weight loss goals are tion and interpretation of
although they are highly recommended not met through diet and exercise
remission in type 2 diabe-
tes. Diabetes Care.
only for patients with nephropathy. modifications alone, pharmacologic 2021;44:2438-2444.
Because of the risk for angioedema and options, including GLP-1RAs and GIP-1
[PMID: 34462270]
77. Samson SL, Vellanki P,
the overall safety profile of ACEIs, ARBs agonists, and surgical options should Blonde L, et al. American
Association of Clinical
may be preferred (60). Multiple BP be offered in medically eligible patients Endocrinology consensus
agents may be needed to achieve con- as part of a comprehensive weight man- statement: comprehen-
sive type 2 diabetes man-
trol, as the average effect is about 10/ agement treatment plan. Management agement algorithm—2023
5 mm Hg per drug class (61). Additional of obesity is reviewed in the In the Clinic update. Endocr Pract.
2023;29:305-340.
information on the management of on obesity (15). [PMID: 37150579]

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 Table 3. Other Clinical Interventions to Reduce Diabetic Complications

Clinical Intervention Approaches

Cardiovascular risk reduction

Smoking cessation (57) Counsel using evidence-based approaches
Consider referral to smoking cessation resources (e.g., counselors, state-
run programs)
Hypertension control (58–62) Goal of <130/80 or <140/90 mm Hg
ARBs and ACEIs highly recommended for patients with nephropathy
Lipid-lowering agents (58, 63–65) High-intensity statin recommended for secondary prevention of ASCVD
and in populations at high ASCVD risk to target LDL-C level <55 mg/dL
(<1.4 mmol/L); add ezetimibe or PCSK9 inhibitor if necessary
At least moderate-intensity statin recommended for most other patients
with T2D (age >40 y) to target LDL-C reduction of ≥50% from baseline
and level <70 mg/dL (<1.8 mmol/L) for primary prevention
Consider bempedoic acid or PCSK9 inhibitor if unable to tolerate statins
Consider annual measurement of lipid panel to improve low long-term
prescription adherence
Weight management (15) Screen for and treat overweight or obesity (based on BMI)
Treatment includes intensive lifestyle modification as cornerstone
Consider pharmacologic therapy in patients with BMI >27.5 kg/m2 (>25
kg/m2 in Asian patients) and/or surgical weight loss options in medically
eligible patients (BMI >35 kg/m2 [>30 kg/m2 in Asian patients] or BMI
>30 kg/m2 [>27.5 kg/m2 in Asian patients] with poor glycemic control)
Consider referral to lifestyle medicine and obesity medicine specialists
Aspirin therapy (66, 67) Recommended for secondary prevention for heart disease (75–325 mg/d)
Shared decision-making conversation recommended for primary preven-
tion (75–162 mg/d)

Screening for diabetic complications and comorbidity

Heart failure screening (58) Screen for heart failure at least once in asymptomatic people with T2D by
measuring natriuretic peptide level
Peripheral artery disease screening (58) Screen using ankle–brachial index at least once for people with T2D aged
≥50 y with T2D duration ≥10 y, microvascular disease, end-organ dam-
age from T2D, or foot complications
Nephropathy measurement (18) Urinary microalbumin–creatinine ratio and estimated glomerular filtration
rate at least annually
Retinal examination (18) Dilated and comprehensive eye examination by ophthalmologist/optom-
etrist or via retinal photography at least every 1–2 y depending on under-
lying risk
Diabetic foot examinations (18) At least annually
Mental health screening and treatment (18) Screening for depression, anxiety, and disordered eating at least annually
Cognitive behavioral therapy, mindfulness-based therapies, and collabo-
rative care; antidepressant therapy

ACEI ¼ angiotensin-converting enzyme inhibitor; ARB ¼ angiotensin receptor blocker; ASCVD ¼ atherosclerotic cardiovascular dis-
ease; BMI ¼ body mass index; LDL-C ¼ low-density lipoprotein cholesterol; PCSK9 ¼ proprotein convertase subtilisin/kexin type 9;
T2D ¼ type 2 diabetes.

Aspirin therapy (75 to 162 mg/d) The ADA also recommends scree- Management of other diabetic
for primary prevention of CVD ning for heart failure in asymptom- complications and comorbidities
may not benefit all patients with atic people with T2D by meas- Optimal care also includes screen-
T2D. An RCT of aspirin in patients uring natriuretic peptide at least ing for and management of ne-
with T2D found an absolute re- once. In addition, the ADA recom- phropathy, retinopathy, and neu-
duction in serious vascular events mends screening for asymptom- ropathy and foot care. Detection
of 1.1% but an increase in bleed- atic peripheral artery disease at of early diabetic nephropathy in-
ing risk of 0.9% (66). Thus, shared least once using an ankle–brachial cludes annual measurement of the
decision making is recommended index in people with T2D who are urinary microalbumin–creatinine ra-
when considering aspirin for pri- aged 50 years or older or have tio (for example, random urine albu-
mary prevention (67). In contrast, 75 T2D duration of at least 10 years, min–creatinine ratio) and estimated
to 325 mg of aspirin per day should microvascular disease, end-organ GFR. Albuminuria is a risk factor for
be recommended for patients with damage from T2D, or foot compli- CVD, and RCTs have shown that
a history of heart disease. cations (58). treatment of albuminuria with ARBs

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or ACEIs reduces progression to least once a year to review dia- with a GFR below 30 mL/min/
end-stage renal disease (68, 69). betes self-management, assess 1.73 m2. Earlier referral can be
As discussed, some GLP-1RAs HbA1c and CVRFs, and manage considered, especially if the origin
(39, 42) and SGLT2-Is (36, 37) and prevent diabetic complica- of renal insufficiency is unclear.
improve renal disease outcomes tions (18). Experts consider quar- Podiatric evaluation is helpful for
and are recommended for mac- terly visits and monitoring of management of lesions, such as
roalbuminuria by the ADA. In HbA1c levels reasonable (18). For calluses or deformities, which
addition, among patients with healthy patients with stable dis- require intervention to reduce risk
T2D and CKD, an RCT has iden- ease, this can be reduced to ev- for foot ulcers and amputation.
tified that finerenone reduced ery 6 to 12 months (18). The
risk for CKD progression and CV National Committee for Quality Referral to mental health special-
events compared with placebo Assurance (NCQA) recommends ists (therapists, counselors, psy-
(70). Retinal examination and at least 1 HbA1c test each year as chologists, psychiatrists) may be
treatment reduces incidence of a quality measure benchmark helpful for patients with comorbid
vision loss in patients with T2D (Appendix Table 3, available at mental health problems, which
(18). Neuropathy screening and Annals.org). can negatively affect self-manage-
foot care are essential in reducing ment and medication adherence
When should a specialist be and increase risk for diabetic
risk for amputation (18). Painful
consulted? complications if untreated.
neuropathy can be treated with
Several specialists could be con-
various agents, including antiepi- When should patients with T2D
sulted to help optimize T2D
leptic agents (carbamazepine, be hospitalized?
management. Referral for formal
gabapentin, pregabalin), duloxe- Patients with severe, symptomatic
diabetes self-management edu-
tine, capsaicin cream, and tricyclic hyperglycemia may require hos-
cation and support programs is
antidepressants. pitalization. Hyperglycemic and
recommended for all patients
Patients with T2D have higher with newly diagnosed T2D, as normoglycemic diabetic ketoaci-
rates of mental health problems well as periodically for reinforce- dosis (defined by presence of
(18). The ADA recommends an- ment; these programs are cov- metabolic acidosis, ketones in se-
nual screening for depression, ered by most insurance but are rum or urine, and hyperglycemia)
anxiety, and disordered eating underused (74). and hyperosmolar coma require
in patients with T2D (18). The hospitalization. Diabetes compli-
Consultation with an endocrinol- cations may require hospitaliza-
USPSTF also recommends rou-
ogist is helpful when diagnostic tion; for example, hypoglycemia,
tine screening for depression in
issues arise or to assist with glu- cellulitis, or osteomyelitis may
patients aged 12 years or older
(71). In addition to antidepres- cose management (for example, require medication adjustments,
sant pharmacologic therapy, evi- in patients with highly labile intravenous antibiotics, or sur-
dence suggests cognitive beha- blood glucose levels), including gery, respectively. Detailed evalu-
vioral therapy and mindfulness- during and in preparation for ation and management of hyper-
based therapies can benefit pregnancy, as poor glycemic glycemia in hospitalized patients
patients with T2D. In particular, control is associated with ad- will be reviewed in an upcoming
integrating primary care and be- verse fetal outcomes (50). In the Clinic on inpatient manage-
havioral health in a collaborative Referral to lifestyle medicine and ment of hyperglycemia.
care model has been shown to obesity medicine specialists may Can T2D go into remission?
improve depression symptoms be helpful in patients with co-
T2D is a heterogeneous disease
and glycemic control (72). Scree- morbid overweight and obesity.
that results from variable expres-
ning and management of depre- Referral for bariatric surgery may
sions of genetic and environ-
ssion are also discussed in the In be appropriate for medically eli-
mental factors and can remit
the Clinic on depression (73). gible patients (75).
under certain circumstances. A
How frequently should A dilated and comprehensive eye consensus report published in
physicians see patients with examination by an ophthalmolo- 2021 on behalf of the Endocrine
T2D, and what should be gist or optometrist or via retinal Society, the European Asso-
included in follow-up visits? photography should be done ev- ciation for the Study of Diabetes,
The ADA recommends physi- ery 1 to 2 years. Nephrologic eval- Diabetes UK, and the ADA pro-
cians see patients with T2D at uation is required for patients posed standardized parameters

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in which patients with an HbA1c HbA1c level below 6.5% at least 3 surgery) (76). Patients who have not
level below 6.5% (<48 mmol/ months after cessation of glu- been using pharmacotherapy for 3
mol) can be considered to be in cose-lowering pharmacotherapy months and have decreased HbA1c
“remission.” For patients using (or ≥3 months after surgery and through lifestyle changes can be
glucose-lowering pharmacother- cessation of pharmacotherapy for considered to be in remission after
apy, remission is defined as an those who have had bariatric at least 6 months of lifestyle change.

Treatment... The goal of treating T2D is to achieve individualized glycemic targets based on underlying risk, life
expectancy, and patient preferences. Patients should achieve at least moderate control (HbA1c level <8.0% in
most cases) to minimize hypoglycemia and because microvascular risk increases exponentially above this level.
More aggressive targets (such as <7.0%) should be reserved for patients with a long life expectancy because
reductions in advanced diabetes complications take 15 to 20 years to accrue.

CLINICAL BOTTOM LINE

Practice Improvement
What measures do U.S. What do professional orga- applicable, we have discussed or
stakeholders use to evaluate the nizations recommend regar- referenced the ADA and other
quality of care for patients with ding care of patients with T2D? relevant guidelines throughout
T2D? Several professional associations this review. ACP conducts sys-
publish guidelines on various tematic evidence reviews to inform
The NCQA, through the Health-
aspects of diabetes care, and guidelines on glucose manage-
care Effectiveness Data and ment in patients with T2D (32, 43)
Information Set program, rec- these vary slightly. The ADA con-
tinually updates its standards of and BP control, which differ from
ommends several measures of the ADA in some respects (59).
diabetes care, which are com-
diabetes care (Appendix Table prehensive and encompass most The American Association of Clini-
3). In 2022, these were sepa- relevant areas of screening, pre- cal Endocrinology updated its gui-
rated and became standalone vention, and management (3, 18, delines in 2023 (77). The USPSTF
measures. It is important to note 21, 33, 50, 55, 58, 75). Our rec- recommendation on screening for
that these recommendations do ommendations are generally elevated blood glucose (not spe-
not align perfectly with clinical consistent with the ADA diabetes cifically diabetes) is similar to the
targets. screening guideline (3). Where ADA guidelines (2, 4).

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 Patient Information
In the Clinic https://medlineplus.gov/diabetestype2.

Tool Kit html

https://medlineplus.gov/languages/
diabetestype2.html
Information on type 2 diabetes in English
and other languages from the National
Type 2 Diabetes Institutes of Health’s MedlinePlus.

www.niddk.nih.gov/health-information/
diabetes/overview
www.niddk.nih.gov/health-information/
informacion-de-la-salud/diabetes/
informacion-general
Overview of diabetes in English and
Spanish from the National Institute of
Diabetes and Digestive and Kidney
Diseases.

https://professional.diabetes.org/clinical-

In the Clinic
support/patient-education-library
Patient education library in English and
other languages from the American
Diabetes Association.
Information for Health Professionals
www.acpjournals.org/doi/10.7326/M23-
2788
American College of Physicians clinical
guideline on newer pharmacologic treat-
ments in adults with type 2 diabetes.

https://diabetesjournals.org/care/issue/47/
Supplement_1
Standards of Care in Diabetes—2024 from
the American Diabetes Association.

http://diabetes.acponline.org
The latest information on type 2 diabetes
from ACP Diabetes Monthly.

www.niddk.nih.gov/health-information/
communication-programs/ndep/health-
professionals
Information on diabetes from the National
Institute of Diabetes and Digestive and
Kidney Diseases.

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 WHAT YOU SHOULD KNOW In the Clinic
Annals of Internal Medicine
ABOUT TYPE 2 DIABETES
What Is Type 2 Diabetes?
Diabetes is a common condition where there is too
much glucose (sugar) in your blood. Insulin is a
hormone that turns sugar into energy. Most peo-
ple with diabetes make some insulin, but it does
not work as well to keep the blood sugar under
control. This is called type 2 diabetes. High sugar
levels in your blood over time may lead to:
• Vision loss
• Kidney damage
• Nerve damage
• Foot ulcers
• Heart disease
• Possible amputation from infections
• Your doctor will check your blood pressure, cho-
What Are the Signs and Symptoms? lesterol levels, and kidney function.
• You will need an eye examination to check for
•Extreme thirst and/or hunger any problems.
•Fatigue
•Frequent need to urinate How Is It Treated?
•Unusual weight loss
• People with diabetes need to improve blood glu-
•Blurred vision
cose control in their bodies.
•Tingling or numbness in the hands or feet • Lifestyle changes, such as losing weight and exer-
Most people with diabetes may not have symp- cising regularly, improve glucose control without
toms at first and will not know they have the medication.
disease. • If lifestyle changes do not improve glucose con-
What Are Other Risk Factors? trol, you may need medicine.
• There are many different types of medicines for
• Age 45 years or older type 2 diabetes, including several new oral and
• African American, Hispanic, Asian, Pacific injectable medicines. Not all people with type 2
Islander, or Native American race or ethnicity diabetes need to take injections or check their
• Overweight or obesity blood sugar at home.

Patient Information
• Having a close relative with type 2 diabetes • Talk to your doctor about the treatment plan that
• A history of diabetes in pregnancy is best for you and what your average blood
Can I Prevent It? sugar target (HbA1c level) should be.
• Make sure your blood pressure and cholesterol are
A healthy diet and regular exercise may prevent controlled to help prevent complications of diabetes.
type 2 diabetes. Even a small amount of weight • The best treatment plan for you is one that you can
loss and 30 minutes of exercise a day can reduce afford and will stick with. Talk about the cost and
your risk for developing diabetes. convenience of treatment plans with your doctor.
How Is It Diagnosed? Questions for My Doctor
• Your doctor will ask you about your medical his- • Do I need to change my diet and start exercising?
tory, including your current diet and exercise reg- • What is an optimal blood sugar target (HbA1c
imen, and do a physical examination. level) for me?
• Diabetes is diagnosed by measuring the level of • Do I have to check my blood sugar? When and
glucose in your blood. You may need to fast how often?
before some diabetes tests. • What are the symptoms of low blood sugar?
• Your hemoglobin A1c (HbA1c) level can be checked What should I do when I have those symptoms?
via a simple blood test that measures your average • How should I care for my feet?
blood sugar over the past 3 months and does not • How often should I have follow-up visits?
require fasting. • Do I need to see other medical specialists?

For More Information

American Diabetes Association
www.diabetes.org/diabetes/type-2

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Appendix Table 1. Recommended Foods and Diets for Type 2 Diabetes

Foods
Nonstarchy vegetables
Fruits
Whole grains
Low-fat dairy products
High-fiber foods
Lean proteins (avoid red and processed meats)
Fatty fish
Nuts and seeds
Minimal added sugars
Minimally processed foods

Diets
DASH (Dietary Approaches to Stop Hypertension)
Mediterranean diet
High-fiber
Low-fat
Low-carbohydrate
Whole-foods plant-based
Vegetarian
Vegan

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Appendix Table 2. Onset and Mechanisms of Action of Various Types of Insulin*

Class Name Peak of Action Duration of Dosage Forms/Product

Action

Rapid-acting (analogues) Lispro 0.5–3 h 3–5 h U-100, U-200

Aspart Prefilled pen, cartridge, vial
Glulisine
Inhaled insulin
Short-acting (human) Regular U-100 2–5 h Up to 12 h U-100
Prefilled pen, vial
Intermediate-acting (human) NPH 4–12 h Up to 24 h U-100
Prefilled pen, vial
Concentrated human Regular U-500 6–8 h Up to 24 h U-500
regular Prefilled pen, vial
Long-acting (analogue) Glargine Relatively peakless Up to 24–42 h U-100, U-200
Detemir Prefilled pen, vial
Degludec
Ultra-long-acting Glargine U-300 Relatively peakless Up to 5 d to U-300
steady state Prefilled pen
Human insulin mixtures 70% NPH/30% regular 2–12 h Up to 24 h U-100
50% NPH/50% regular 2–5 h Prefilled pen, vial
Analogue mixtures 75% lispro protamine/25% 1–2 h Up to 24 h U-100
lispro Prefilled pen, vial
50% lispro protamine/50% 1–2 h
lispro
70% aspart protamine/30% 1–4 h
aspart

NPH ¼ neutral protamine Hagedorn.

* Data are from reference 33.

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Appendix Table 3. Quality Measures for Diabetes

HbA1c management
Percentage of patients who have had ≥1 HbA1c test in the measurement year

HbA1c management control

Percentage of patients whose most recent HbA1c level was >9.0% (poor control)
Percentage of patients whose most recent HbA1c level was <8.0% (control)

Blood pressure management

Percentage of patients whose most recent blood pressure was <140/90 mm Hg

Eye examination
Percentage of patients who received a retinal or dilated eye examination by an eye care professional (optometrist or
ophthalmologist) in the measurement year or had a negative retinopathy screening result in the prior year

Medical attention for nephropathy

Percentage of patients with screening for albuminuria, use of an ACEI/ARB, or documentation of medical attention for kidney
disease in the measurement year

ACEI ¼ angiotensin-converting enzyme inhibitor; ARB ¼ angiotensin receptor blocker; HbA1c ¼ hemoglobin A1c.

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