Medication Profiles of Antihyperglycemic Medications

Sodium Glucose Secretagogues

Glucagon-like Peptide 1 Cotransporter 2 Inhibitors Dipeptidyl Peptidase 4 Thiazolidinediones
SU GLN
Metformin Receptor Agonists (GLP1 RAs) (SGLT2is) Inhibitors (DPP4is) (TZDs)* Insulin
Moderate /
Hypoglycemia Neutral Neutral Neutral Neutral Neutral Mild Moderate to severe
severe
Loss
Weight Slight loss Semaglutide > liraglutide > dulaglutide > Loss Neutral Gain Gain Gain
exenatide > lixisenatide
Exenatide not indicated if CrCl Not indicated for eGFR <45 Dose adj necessary
Contraindicated if eGFR <30 mL/min Genital mycotic infections (except linagliptin)
Renal / GU Neutral More hypoglycemia risk More hypoglycemia risk
<30 Possible benefit of Effective in reducing
Possible benefit of liraglutide albuminuria
empagliflozin
GI AEs Moderate Moderate Neutral Neutral Neutral Neutral Neutral
Possible benefit of Possible risk for
Cardiac—CHF Neutral Moderate More CHF risk More CHF risk
empagliflozin saxagliptin and alogliptin
Neutral
May reduce stroke
Cardiac—ASCVD Possible benefit of LA GLP1 RA Possible CV benefit Neutral Possible ASCVD risk Neutral
risk
Moderate fracture
Bone Neutral Neutral Canagliflozin warning Neutral Neutral Neutral
risk
Ketoacidosis Neutral Neutral Neutral Neutral Neutral Neutral Neutral
Efficacy High High Intermediate Intermediate (target PPG) High High
Administration Oral Injectable Oral Oral Oral Oral Injectable
Cost Variable High High High Low Low
HbA1c above target: Preferred initial • Consider early introduction if:
pharmacologic agent plus − evidence of ongoing catabolism
comprehensive lifestyle − hyperglycemia symptoms
(weight management and − A1C levels (>10%) or BG levels
physical activity) ≥300 mg/dL
• Consider dual therapy in newly
diagnosed T2DM with an A1C ≥1.5%
above their glycemic target
If A1C remains above target despite recommended AND NO ASCVD OR CKD
first-line treatment
PLUS ESTABLISHED ASCVD or CKD
and ASCVD PREDOMINATES → GLP1 RA with proven CV benefit SGLT2 inhibitor with proven CV
(Liraglutide > semaglutide > benefit, if eGFR adequate
dulaglutide) (empagliflozin > canagliflozin >
dapagliflozin)
and HF or CKD PREDOMINATES → AND SGLT2 inhibitor is not tolerated, SGLT2 inhibitor with proven CV
is contraindicated, or eGFR is less benefit, if eGFR adequate
than adequate, add a GLP1 RA with (empagliflozin > canagliflozin)
proven CV benefit (Liraglutide >
semaglutide > dulaglutide)
ASCVD = atherosclerotic cardiovascular disease; CHF = congestive heart failure; CrCl = creatinine clearance; DKA = diabetic ketoacidosis; DPP4is = Dipeptidyl Peptidase 4 Inhibitors; eGFR = estimated glomerular filtration rate; GLN = glinide (meglitinides);
GLP1 RAs = Glucagon-like Peptide 1 Receptor Agonists; GU = Genitourinary; Met = Metformin; SGLT2 = sodium glucose cotransporter 2; SU = sulfonylurea; T2D = type 2 diabetes; TZDs = Thiazolidinediones

Few adverse events or possible benefits Use with caution Likelihood of adverse effects ? Uncertain effect

American Diabetes Association. 9. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes—2021. Dia Care. 2021;44(Supplement 1):S111-S124. doi:10.2337/dc21-S009
Garber AJ, Handelsman Y, Grunberger G, et al. Consensus statement by the american association of clinical endocrinologists and american college of endocrinology on the comprehensive type 2 diabetes management
algorithm – 2020 executive summary. Endo Pract. 2020;26(1):107-139. doi:10.4158/CS-2019-0472