Diabetes Mellitus: Oral Hypoglycemic Drugs ( a practical step-up approach )

Start with Metformin 500 mg once a day to maximum 1000 mg twice a day; take with meals; hold if CrCl< 30 ml/min/1.73 m2.

If HbA1C target not reached after 3 months, add one of-

- Sulfonylureas: Glimepiride 1 mg to max 4 mg/day, with breakfast or first main meal of the day. Beware in elderly patient as risk of hypoglycemia

- SGLT2 inhibitor: Empagliflozin 10 mg once daily in the morning, with or without food. Prefer in patients with ASCVD, heart failure or diabetic kidney disease.

- DPP-4 Inhibitor: Linagliptin 5 mg once daily, may be administered with or without food. Linagliptin can be used without dose adjustment in renal impairment, including ESRD.

- Thiazolidinediones: Pioglitazone 15 to 30 mg once daily; may be administered without regards to meal; beneficial in NAFLD. Serious side effects include worsening heart failure, increase bone fracture risk. 

If HbA1C target not reached after 3 months, add another drug of different group from the above list as per patient comorbidity and safety profile.

If goal not reached after 3 oral hypoglycemic drugs, add insulin. 

Note: Start with dual therapy if HbA1C > 9% on initial presentation. Begin insulin therapy for HbA1C > 10 % or blood glucose > 300 mg/dl at initial presentation.

HbA1C targets:

 < 7%- Most of non-pregnant adults

< 8%- history of severe hypoglycemia, limited life expectancy, advanced micro or macrovascular complications.

References:

1. ADA Standards of Medical Care in Diabetes- 2020

2. Pocket Primary Care 2nd Edition. 2018

3. Uptodate 2021