Diabetes Mellitus: Pharmacotherapy- Gliptins and a-Glycoside Inhibitors!

 PHARMACOTHERAPY: 

Medications classifications include:

1.  Sulfonyl Urea's
2. Nonsylfonylurea Secretagogues (a-Glinides)
3. Biguanides
4. Thiazolidinediones
5. a-Glucosidase Inhibitors
6. Dipeptidyl Peptidase-4 Inhibitors (Gliptins)
7. Sodium-glucose co-transporter (SGLT) Inhibitors 
8. Central-Acting Dopamine Agonists
9. Bile Acid Sequestrants
10. Insulin therapy

5. a-GLUCOSIDASE INHIBITORS

• Acarbose and Miglitol are a-glucosidase inhibitors currently approved in the United States.

Mechanism of Action:

• An enzyme that is along the brush border of the intestine cells called a-glucosidase; breaks down the complex carbohydrates into simple sugars, resulting in absorption. The a-glucosidase inhibitors work by delaying the absorption of carbohydrates from the intestinal tract, which reduces the rise in postprandial glucose levels.

Therapy:

As a monotherapy, a-glucosidase inhibitors primarily reduce post-prandial glucose excursions. 

Clinical Use:

FPG concentrations have been decreased by 40-50mg/dL and A1c levels are decreased by 0.3%-1%.

Adverse Effects:

• High incidences of GI Upset such as Flatulence, abdominal discomfort, and diarrhea. 
• GI effects occur as a result of intestinal bacteria in the distal gut metabolizing undigested carbohydrates and producing carbon dioxide and methane gas.

Contraindications:

Contraindicated in patients with;

• short bowel syndrome
• Inflammatory Bowel Disease
• In patients with serum creatinine greater than 2mg/dL.

6. DIPEPTIDYL PEPTIDASE-4 INHIBITORS (GLIPTINS)

• Drugs included mostly are Sitagliptin, Saxagliptin and Linagliptin.
• These are approved as adjunct to diet and exercise to improve glycemic control in adults with T2DM.

Mechanism of Action:

• These agents lower the blood glucose levels by inhibiting DPP-4; the enzyme that degrade endogenous GLP-1(Incretins). DPP-4 Inhibitors increase the amount of endogenous GLP-1.

Clinical Use:

• Used primarily to decrease postprandial blood glucose levels.
• Typical A1c reductions are 0.7-1%.

Adverse effects:

• Headache
• Nasopharyngitis
• Hypoglycemia

Dose Adjustments:

Sitagliptin: Dosage adjustments for 50-25mg/day are recommended for patients with moderate and severe renal impairment, respectively.

Saxagliptin: should be dosed at 2.5mg/day with creatinine clearance less than 50ml/min or if strong CYP3A4/5 inhibitors are being used concomitantly.

Linagliptin: is a substrate of CYP3A4 is dosed at 5mg/day and requires no adjustment for renal or hepatic impairment.