Diabetes Medications

Drug Names Mechanism of Action Dosage, Frequency, Administration Side Effects Warnings/Contraindications
Biguanide

IR:
•​ GFR 30-45: do not initiate or dose reduce 50%
•​ ↓ hepatic gluconeogenesis •​ Start 500 mg PO daily or BID, or 850 mg PO daily
if already on therapy
•​ ↓ intestinal glucose •​ Titrate by 500-850 mg weekly to avoid GI SEs
•​ GI upset (diarrhea, N/V) •​ GFR < 30: contraindicated
Metformin absorption •​ Max 2.55g/ day (consider TID if > 2g/day)
•​ Vitamin B12 deficiency •​ BBW: lactic acidosis
(Glucophage) •​ Improve insulin sensitivity (↑ ER:
•​ Lactic acidosis •​ Hold before iodinated contrast imaging if GFR
peripheral glucose uptake •​ Start 500-1000 mg PO daily
30-60, hepatic disease, alcoholism, or heart
and utilization) •​ Titrate by 500 mg weekly to avoid GI SEs
failure
•​ Max 2g/day (may consider BID)

Sulfonylurea

•​ Glyburide has long t ½ d/t active metabolites

Glyburide
•​ Glyburide: 1 mg PO daily, titrate by 2.5 mg weekly to •​ Eliminated renally
(Diabeta,
max 20mg/day •​ Avoid use CrCl < 50
Glynase)
•​ Inhibit the ATP-K channel on •​ Glyburide mean A1c reduction 0.85-1.27
•​ Hypoglycemia
beta cells, which causes
Glipizide •​ Glipizide: 2.5-10 mg PO 30 min before breakfast, max •​ Weight gain •​ In CKD, prefer glipizide or glimepiride d/t
insulin secretion
(Glucotrol) 40 mg daily (but no efficacy > 20 mg) •​ Skin rash hepatic metabolism
•​ Stimulates pancreas to
•​ GI upset •​ Glimepiride mean A1c reduction 0.85-1
Glimepiride release insulin for several •​ Glimepiride: 1-2 mg PO with breakfast (1 mg if older
•​ Irritability •​ Glipizide mean A1c reduction 0.95
(Amaryl) hours after a meal or CKD). titrate to 2-4 mg PO daily

Gliclazide •​ Gliclazide: 40- 80 mg PO daily (40 mg If older or

(Diamicron) CKD). titrate to 40-320 mg daily (BID if > 160 mg)

Glucagon-like Peptide-1 Receptor Agonist (GLP-1 RA)

Liraglutide •​ Start with 0.6 mg daily x 1 week, then 1.2 mg daily
•​ No renal or hepatic dose adjustment
(Victoza) •​ May increase to 1.8 mg daily if inadequate control

•​ start with 0.75 mg SQ once a week, w/ or w/o meals

Dulaglutide •​ ~1.5 % A1c reduction
•​ Promotes insulin secretion •​ Increase to 1.5 mg SQ once a week if inadequate •​ Nausea
(Trulicity) •​ No renal or hepatic dose adjustment
in a glucose dependent glycemic response •​ Weight loss
manner; binds to GLP1 •​ GI upset
•​ Start with 5 mg SQ BID within 1 hr prior to AM and
receptors on beta cells to •​ Injection site reactions
Exenatide PM meals
activates adenylate cyclase •​ Sinus tachycardia (dulaglutide) •​ Avoid in CrCl < 30 ml/min
(Byetta) •​ May increase to 10 mcg BID after a month for better
→ production of cAMP from •​ URTIs (liraglutide)
glycemic control
ATP → promote insulin •​ Headache
Exenatide ER secretion
•​ 2 mg once weekly anytime of day w/ or w/o meals •​ Avoid in CrCl < 30 ml/min
(Bydureon) •​ Slows gastric emptying
Lixisenatide •​ ↓ hepatic gluconeogenesis, •​ 10 mcg SQ x 2 weeks, then 20 mcg daily •​ Caution in mild-moderate renal impairment,
(Adlyxin) •​ give within 1 hr prior to first meal of the day but avoid in ESRD
•​ Start with 0.25 mg SQ weekly any time of day w/ or
Semagultide •​ increased serum amylase and
w/o meals •​ No renal or hepatic dose adjustment
(Ozempic) lipase
•​ increase to 0.5 mg weekly after 4 weeks
 Dipeptidyl Peptidase-4 (DPP-4) Inhibitor
•​ mean ↓ in A1C from 0.4-0.6% •​ DDI with Dig: 11% ↑ in AUC and plasma Cmax
•​ Nasopharyngitis/URIs (18%) of digoxin at 0.25 mg/day. Dose
Sitagliptin
•​ 100 mg once daily (if CrCl < 30, 25 mg once daily) •​ Headache adjustment of digoxin not recommended, but
(Januvia) •​ Inhibits dipeptidyl peptidase
•​ N/D/abd pain monitor closely.
IV (DPP-IV) enzyme resulting
•​ UTIs •​
in prolonged active incretin
•​ Weight neutral •​ Max dose is 2.5mg once daily when
Saxagliptin levels resulting in increased
•​ 2.5 - 5 mg once daily (if CrCl < 50, 2.5 mg once daily) •​ Rare: co-administered with strong CYP450 3A4/5
(Onglyza) insulin synthesis & release
○​ Acute pancreatitis inhibitors.
and decreased glucagon
Linagliptin ○​ SJS
secretion •​ 5 mg once daily •​ Only one not requiring renal dose adjustment
(Tradjenta) ○​ Anaphylaxis
•​ (since DPP-4 normally
•​ FDA alert in 2015 warning that
metabolizes GLP-1 and GIP)
Alogliptin •​ 25 mg once daily (if CrCl 30-60, 12.5mg once daily; if DPP-4 I can cause severe and
•​
(Nesina) CrCl < 30, 6.25 mg once daily) disabling joint pain

Sodium-Glucose Transporter-2 (SGLT-2) Inhibitor

•​ 100 mg once daily prior to first meal; may increase to
300 mg if eGFR ≥ 60
•​ Concomitant UGT transporter inducers (rifampin, •​ Canagliflozin ↑ risk of amputation and
pheny, phenob, ritonavir): increase to 300 mg once fracture
Canagliflozin daily in patients currently tolerating canagliflozin 100 •​ In patients with ASCVD on metformin,
(Invokana) mg once daily with eGFR ≥60 and require additional addition of canagliflozin may be considered to
control. reduce major adverse cardiovascular events,
•​ If concurrent UGT enzyme inducers and eGFR 45-60 based on drug-specific and patient factor
consider alternate therapy
•​ Admin with or without food

•​ Initial: 5 mg once daily; may increase to 10 mg

Dapagliflozin •​ eGFR 30-60: not recommended for initiation of
•​ Weight loss •​
(Farxiga) •​ Inhibits the SGLT-2 therapy or when eGFR is persistently in this range
•​ eGFR <30: contraindicated. •​ Hypotension / dizziness
transporter in the kidneys,
•​ Genitourinary fungal infections
preventing glucose
•​ Initial: 10 mg once daily; may increase to 25 mg •​ UTI / polyuria
reabsorption and increasing
•​ eGFR 30 - 45: recommend not initiate therapy / •​ ↑ LDL and transient ↑ Scr
glucosuria
discontinue when eGFR is persistently <45. •​ Nasopharyngitis
•​ In patients with ASCVD on metformin,
Empagliflozin •​ EMPA-REG OUTCOME trial: empagliflozin in DM+
empagliflozin is a preferred add-on agent to
(Jardiance) CVD and renal impairment (eGFR 30-60) may be
reduce major adverse CV events
associated with decreases in incident or worsening
nephropathy and decreased CV mortality.
•​ eGFR < 30 contrainidicated

•​ Start 5 mg once daily; may increase to max 15 mg

•​ Warning - bone fractures, genital mycotic
(admin in morning w/o regard to meals)
infections, hypotension, ketoacidsosis, lower
Ertugliflozin •​ eGFR 30-60: Not recommended for initiation of
limb amputation, LDL abnormality, nec fasc,
(Steglatro) therapy in preexisting impairment or continued use if
AKI, UTIs, not studied in severe hepatic
persistent
impairment
•​ eGFR < 30: contraindicated.
 Thiazolidinedione (TZDs)
•​ Initial: 15 - 30 mg once daily; patients with HF NYH •​ BBW: cause or exacerbate CHF in some
Class I or II should start with 15 mg once daily. patients - not recommended for pts with
•​ Titration: Based on HbA1c, dose may be increased in symptomatic HF.
Pioglitazone 15 mg increments up to a max 45 mg once daily; •​ CI: in patients with established NYHA class III
monitor closely during titration for ADEs or IV HF
•​ Dose adjust with CYP2C8 inhibitors (gemfibrozil): •​ Measure LFTs if hepatic impairment during
Max 15 mg once daily therapy:
○​ If an alternative etiology not
identified and ALT >3 x ULN:
Do not reinitiate
•​ Agonists for peroxisome ○​ If an alternative etiology is
•​ Weight gain
proliferator-activated identified but < 3x ULN or total
•​ Edema
receptor-y (PPAR-y) which bilirubin <2 x ULN: reinitiate
•​ Hypoglycemia
influences production of a with caution
•​ Headache
products involved in glucose •​ Initial: 4 mg/day as a single dose or BID If response is •​ Warning/Precaution:
•​ S/sx of HF
and lipid metabolism inadequate after 8-12 weeks of treatment, may ○​ Bladder cancer
Rosiglitazone increase to max 8 mg/day. ○​ Edema
•​ Some data suggests 4 mg BID may lower fasting ○​ Fracture
plasma glucose and HbA1c more effectively ○​ HF
○​ Heme / hepatic effects
○​ hypoglycemia
○​ macular edema
○​ IHD (rosiglitazone)
•​ CVOT: Meta-analysis compared rosiglitazone
with placebo → rosiglitazone a/w statistically
significant increased risk of MI