Mechanism of Action of DPP-4 Inhibitors

Mechanism of Action and Pharmacokinetics of Diabetes Medications

• Acarbose and miglitol inhibit intestinal alpha-glucosidases, delaying carbohydrate digestion and absorption.
• Acarbose has a notable characteristic of being minimally absorbed from the gut, with the majority of the dose being excreted in the feces.

Adverse Effects of Diabetes Medications

• Acarbose and miglitol are commonly associated with gastrointestinal adverse effects, such as diarrhea, flatulence, and abdominal pain.
• Patients with inflammatory bowel disease are advised against using acarbose and miglitol due to the risk of exacerbating their condition.

DPP-4 Inhibitors

• Alogliptin, linagliptin, saxagliptin, and sitagliptin are DPP-4 inhibitors, which work by increasing the levels of active incretin hormones, such as GLP-1 and GIP, to improve glucose tolerance.
• The main difference in excretion among DPP-4 inhibitors is that alogliptin is primarily excreted in the urine, linagliptin is primarily excreted in the enterohepatic system, saxagliptin is primarily excreted in the feces, and sitagliptin is primarily excreted in the urine.
• A false statement about DPP-4 inhibitors is that they are associated with a high risk of hypoglycemia.
• Saxagliptin is primarily eliminated via the enterohepatic system.
• The primary route of elimination for saxagliptin is hepatic.
• A common adverse effect not associated with DPP-4 inhibitors is weight gain.
• A rare but serious adverse effect that may occur with the use of DPP-4 inhibitors is angioedema.

SGLT2 Inhibitors

• SGLT2 inhibitors like canagliflozin work by reducing the reabsorption of glucose in the kidney, leading to increased glucose excretion in the urine.
• SGLT2 inhibitors are not indicated for the treatment of hypertension, although they may have a secondary effect of lowering blood pressure.
• Drugs like canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin are metabolized in the body via UGT1A9 and UGT2B7-mediated glucuronidation.
• SGLT2 inhibitors should be avoided in patients with renal dysfunction due to the risk of adverse effects.
• A cardiovascular risk to be considered when using alogliptin and saxagliptin in patients is the risk of cardiovascular death and hospitalization for heart failure.
• Empagliflozin is the only SGLT2 inhibitor with an additional indication to reduce cardiovascular death in patients with type 2 diabetes and cardiovascular disease.