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Antidiabetic drugs

Last updated: October 5, 2020


Antidiabetic drugs (with the exception of insulin) are all pharmacological agents that have been approved for hyperglycemic treatment in type 2 diabetes mellitus (DM). If lifestyle modifications (weight loss, dietary modification, and exercise) do not sufficiently reduce A1C levels (target level: ∼ 7%), pharmacological treatment with antidiabetic drugs should be initiated. These drugs may be classified according to their mechanism of action as insulinotropic or non-insulinotropic. They are available as monotherapy or combination therapies, with the latter involving two (or, less commonly, three) antidiabetic drugs and/or insulin. The exact treatment algorithms are reviewed in the treatment section of diabetes mellitus. The drug of choice for all type 2 diabetic patients is metformin. This drug has beneficial effects on glucose metabolism and promotes weight loss or at least weight stabilization. In addition, numerous studies have demonstrated that metformin can reduce mortality and the risk of complications. If metformin is contraindicated, not tolerated, or does not sufficiently control blood glucose levels, another class of antidiabetic drug may be administered. Most antidiabetic drugs are not recommended or should be used with caution in patients with moderate or severe renal failure or other significant comorbidities. Oral antidiabetic drugs are not recommended during pregnancy or breastfeeding.


Overview of antidiabetic drugs

Class Mechanism of action Side effects Contraindications
Biguanide (metformin)
Sulfonylureas (e.g., glyburide, glimepiride)
Meglitinides (nateglinide, repaglinide)
  • Severe renal or liver failure
DPP-4 inhibitors (saxagliptin, sitagliptin)
  • Inhibit GLP-1 degradation → promotes glucose-dependent insulin secretion
GLP-1 agonists (incretin mimetic drugs: exenatide, liraglutide, albiglutide)
  • Direct stimulation of the GLP-1 receptor
  • Preexisting, symptomatic gastrointestinal motility disorders
SGLT-2 inhibitors (canagliflozin, dapagliflozin, empagliflozin)
Alpha-glucosidase inhibitors (acarbose)
  • Reduce intestinal glucose absorption
  • Gastrointestinal complaints (flatulence, diarrhea, feeling of satiety)
Thiazolidinediones (pioglitazone)
Amylin analogs (pramlintide)
  • Reduce glucagon release
  • Reduce gastric emptying
  • Increase satiety

Common contraindications of antidiabetic agents

Sulfonylureas are associated with the highest risk of hypoglycemia. All other substances do not carry a significant risk of hypoglycemia when used as a monotherapy. Combination therapy, particularly with sulfonylurea, significantly increases the risk of hypoglycemia!

Antihyperglycemic therapy algorithm for type 2 diabetes



Biguanides (metformin)

Active agent

  • Metformin

Clinical profile

Metformin treatment must be paused prior to the administration of a contrast medium or scheduled surgery to reduce the risk of lactic acidosis!

Because of its favorable risk-benefit ratio, metformin is the drug of choice for monotherapy and combination therapy in all stages of type 2 DM!

Thiazolidinediones (glitazones, insulin sensitizers)

Active agents

  • Pioglitazone
  • Rosiglitazone

Clinical profile



Active agents

  • Glyburide: the standard substance of this class with a relatively long half-life
  • Glipizide: a short-acting agent

Clinical profile

Beta-blockers may mask the warning signs of hypoglycemia (e.g., tachycardia) and decrease serum glucose levels even further (→ see hypoglycemia). Since sulfonylureas also increase the risk of hypoglycemia, the combination of these two substances should be avoided!

Meglitinides (sulfonylurea analogue)

Active agents

Clinical profile

Incretin mimetics (GLP-1 receptor agonists)

Active agents

  • Exenatide
  • Liraglutide: rapid-release formula that is administered daily
  • Albiglutide: extended-release formula that is administered once weekly
  • Dulaglutide

Clinical profile


Dipeptidyl peptidase-4 inhibitors (gliptins)

Active agents

  • Sitagliptin
  • Saxagliptin
  • Linagliptin

Clinical profile


SGLT-2 inhibitors (gliflozins)

Active agents

  • Dapagliflozin
  • Empagliflozin
  • Canagliflozin

Clinical profile

Alpha-glucosidase inhibitors

Active agents

  • Acarbose
  • Miglitol

Clinical profile

  • Mechanism of action
    • Inhibits alpha-glucosidase → decreased intestinal glucose absorptionThe drug is particularly effective in controlling postprandial blood glucose levels.
    • The undigested carbohydrates reach the colon, where they are degraded by intestinal bacteria, resulting in the production of intestinal gas.
  • Clinical characteristics
  • Important side effects: gastrointestinal complaints (flatulence, abdominal discomfort, diarrhea)
  • Contraindications

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  1. Jenkins B, McInnis M, Lewis C. Step-Up to USMLE Step 2 CK. Lippincott Williams & Wilkins ; 2015
  2. Dungan K, Hirsch IB, Mulder JE. Amylin Analogs for the Treatment of Diabetes Mellitus. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/amylin-analogs-for-the-treatment-of-diabetes-mellitus.Last updated: September 11, 2017. Accessed: June 18, 2018.
  3. Khardori R. Type 2 Diabetes Mellitus. Type 2 Diabetes Mellitus. New York, NY: WebMD. http://emedicine.medscape.com/article/117853-overview#showall. Updated: January 12, 2017. Accessed: February 13, 2017.
  4. UpToDate. Metformin: Drug information. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/metformin-drug-information.Last updated: January 1, 2017. Accessed: March 9, 2017.
  5. Soghoian S. Disulfiram Toxicity. Disulfiram Toxicity. New York, NY: WebMD. http://emedicine.medscape.com/article/814525-overview. Updated: January 6, 2016. Accessed: February 23, 2017.
  6. Katzung B,Trevor A. Basic and Clinical Pharmacology. McGraw-Hill Education ; 2014
  7. Nesto RW. Heart failure in diabetes mellitus. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/heart-failure-in-diabetes-mellitus.Last updated: November 2, 2015. Accessed: February 23, 2017.
  8. UpToDate. Pioglitazone: Drug information. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/pioglitazone-drug-information.Last updated: January 1, 2017. Accessed: March 9, 2017.
  9. Le T, Bhushan V,‎ Sochat M, Chavda Y, Abrams J, Kalani M, Kallianos K, Vaidyanathan V. First Aid for the USMLE Step 1 2019. McGraw-Hill Medical
  10. Dungan K, DeSantis A. Glucagon-like peptide-1 receptor agonists for the treatment of type 2 diabetes mellitus. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/glucagon-like-peptide-1-receptor-agonists-for-the-treatment-of-type-2-diabetes-mellitus.Last updated: November 21, 2016. Accessed: February 23, 2017.
  11. Hinnen D, Nielsen LL, Waninger A, Kushner P. Incretin mimetics and DPP-IV inhibitors: new paradigms for the treatment of type 2 diabetes. J Am Board Fam Med. 2006; 19 (6): p.612-620.
  12. FDA Drug Safety Communication: FDA investigating reports of possible increased risk of pancreatitis and pre-cancerous findings of the pancreas from incretin mimetic drugs for type 2 diabetes. https://www.fda.gov/Drugs/DrugSafety/ucm343187.htm. Updated: March 14, 2013. Accessed: February 23, 2017.
  13. Dulaglutide. https://www.drugs.com/ppa/dulaglutide.html. Updated: February 23, 2017. Accessed: February 23, 2017.
  14. Liraglutide. https://www.drugs.com/ppa/liraglutide.html. Updated: February 23, 2017. Accessed: February 23, 2017.
  15. FDA Drug Safety Communication: FDA warns that DPP-4 inhibitors for type 2 diabetes may cause severe joint pain. https://www.fda.gov/Drugs/DrugSafety/ucm459579.htm. Updated: August 28, 2015. Accessed: February 23, 2017.
  16. DPP-IV Inhibitors. https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_Diabetes_Guide/547042/all/DPP_IV_Inhibitors. Updated: December 3, 2018. Accessed: January 20, 2019.
  17. Highlights of Prescribing Information - Janumet.
  18. Triplitt C. Drug Interactions of Medications Commonly Used in Diabetes. Diabetes Spectrum. 2006; 19 (4): p.202-211. doi: 10.2337/diaspect.19.4.202 . | Open in Read by QxMD
  19. Sola et al. State of the art paper Sulfonylureas and their use in clinical practice. Archives of Medical Science. 2015; 4 : p.840-848. doi: 10.5114/aoms.2015.53304 . | Open in Read by QxMD
  20. Madiraju et al. Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature. 2014; 510 (7506): p.542-546. doi: 10.1038/nature13270 . | Open in Read by QxMD
  21. American Diabetes Association. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes—2019. Diabetes Care. 2018; 42 (Supplement 1): p.S90-S102. doi: 10.2337/dc19-s009 . | Open in Read by QxMD
  22. Empagliflozin. https://www.drugs.com/ppa/empagliflozin.html. Updated: June 23, 2019. Accessed: September 23, 2019.
  23. Fioretto P, Zambon A, Rossato M, Busetto L, Vettor R. SGLT2 Inhibitors and the Diabetic Kidney. Diabetes Care. 2016; 39 (Supplement 2): p.S165-S171. doi: 10.2337/dcs15-3006 . | Open in Read by QxMD