Choosing Glucose Lowering Therapy in Type 2 Diabetes

Choosing glucose lowering therapy in type 2 diabetes means matching the drug to the patient’s cardiovascular, heart failure and kidney risk, hypoglycaemia risk, weight, cost and local supply, not only to the HbA1c. Organ protection is chosen first when a compelling indication exists, and glucose control is built around it.

Targets. The usual HbA1c target is 53 mmol/mol (7.0%). Use 58 to 64 mmol/mol (7.5 to 8.0%) in frail patients, those with limited life expectancy, or those at high risk of hypoglycaemia. A lower target of 48 mmol/mol (6.5%) suits young patients on drugs that do not cause hypoglycaemia.

Compelling indications. Established atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease with albuminuria or eGFR under 60 mL/min/1.73 m2 favour an SGLT2 inhibitor, a GLP 1 receptor agonist, or both, whatever the HbA1c.

Insulin early. Start insulin when HbA1c exceeds 86 mmol/mol (10%), when glucose is over 16.7 mmol/L with symptoms or weight loss, when ketosis is present, or when oral drugs fail.

Ketosis-prone presentations. Ketosis-prone type 2 diabetes is described in sub-Saharan African populations. Such patients present with ketosis, may later come off insulin, and need clinical judgement rather than rigid labels.

First line. Metformin, unless contraindicated or not tolerated, alongside lifestyle measures.

Add by comorbidity.

Avoid. Glibenclamide in older adults and in chronic kidney disease. Saxagliptin and alogliptin in heart failure. Pioglitazone in heart failure or active bladder cancer.

Combinations. Do not combine a DPP 4 inhibitor with a GLP 1 receptor agonist.

Regional supply. Metformin, gliclazide, glibenclamide, and human insulin are widely stocked in East Africa. SGLT2 inhibitors and GLP 1 receptor agonists are limited mainly by cost; plan therapy around what the patient can sustain.

Representative starting regimens. - Metformin 500 mg orally once daily with the evening meal, titrated to 1 g twice daily. - Empagliflozin 10 mg or dapagliflozin 10 mg orally once daily. - Semaglutide 0.25 mg subcutaneously once weekly for 4 weeks, then 0.5 mg weekly. - Gliclazide 40 mg orally once daily with breakfast. - Sitagliptin 100 mg orally once daily. - Basal insulin 10 units subcutaneously once daily, or 0.1 to 0.2 units/kg.

Stepping up. Review at 3 months. If the HbA1c target is not reached, add or intensify one drug at a time and stop agents that bring no benefit.

Special groups.

• Kidney impairment: metformin stops under eGFR 30; sulphonylureas and insulin need dose reduction; DPP 4 inhibitors except linagliptin need dose reduction.
• Liver disease: insulin is preferred in decompensated cirrhosis; avoid metformin and pioglitazone there.
• Older adults: avoid hypoglycaemia first; relax targets.
• Pregnancy: stop all non-insulin agents except metformin where used; insulin is preferred.
• Children and adolescents with type 2 diabetes: metformin and insulin; GLP 1 receptor agonists are licensed for some ages in some regions.

Monitoring. HbA1c every 3 months until at target, then every 6 months. Annual eGFR, urine albumin to creatinine ratio, lipids, retinal screening, and foot examination. Capillary glucose for patients on insulin or sulphonylureas.

Stopping. Stop a drug that causes severe hypoglycaemia, ketoacidosis, pancreatitis, or serious infection. Stop a GLP 1 receptor agonist if there is no meaningful glucose or weight response by 6 months.

Referral and escalation. Refer to a diabetes specialist for recurrent severe hypoglycaemia, unexplained ketosis, pregnancy or planned pregnancy, rapid HbA1c rise on insulin, or eGFR under 30 mL/min/1.73 m2.