From the Guidelines
The treatment pathway for type 2 diabetes should begin with lifestyle modifications and metformin as first-line pharmacological therapy, with a focus on individualized treatment goals and regular monitoring of HbA1c, kidney function, and cardiovascular risk factors, as recommended by the most recent guidelines 1. The initial treatment approach should include comprehensive lifestyle modification, such as diet, exercise, and weight management, alongside metformin at an initial dose of 500mg once daily, gradually increasing to 1000mg twice daily as tolerated.
- If metformin is contraindicated or not tolerated, alternatives include dipeptidyl peptidase-4 (DPP-4) inhibitors, sulfonylureas, pioglitazone, or sodium-glucose cotransporter 2 (SGLT2) inhibitors, with consideration of the individual's comorbidities, hypoglycemia risk, weight considerations, and patient preferences 1.
- For patients not achieving target HbA1c levels (typically 48-53 mmol/mol or 6.5-7%), dual therapy is recommended by adding a second agent from a different class, with early combination therapy considered to shorten the time to attainment of individualized treatment goals 1.
- If dual therapy is insufficient, triple therapy or combination injectable therapy with GLP-1 receptor agonists or insulin may be initiated, with insulin therapy typically starting with once-daily basal insulin (such as insulin glargine, detemir, or NPH insulin), and potential progression to multiple daily injections if needed.
- Throughout treatment, regular monitoring of HbA1c (every 3-6 months), kidney function, cardiovascular risk factors, and potential medication side effects is essential, with a person-centered shared decision-making approach guiding the choice of pharmacologic agents 1. Key considerations in treatment decisions include the effects on cardiovascular and renal comorbidities, effectiveness, hypoglycemia risk, impact on weight, cost and access, risk for adverse reactions and tolerability, and individual preferences, as outlined in the most recent guidelines 1.
From the Research
Treatment Pathway for Diabetes 2 as per NICE CKS
- The treatment pathway for type 2 diabetes mellitus (T2DM) involves various classes of drugs, including metformin, pioglitazone, DPP-4 inhibitors, GLP-1 receptor agonists, SGLT-2 inhibitors, and sulphonylureas 2, 3, 4.
- Metformin is considered the first-line oral therapy for T2DM, due to its glycaemic benefit and relatively safe adverse effect profile, particularly with avoidance of hypoglycaemia 3.
- Pioglitazone, a thiazolidinedione, can be administered in combination with metformin, sulfonylureas, exenatide, DPP-4 inhibitors, or insulin, and has been shown to improve glycemic control with an extremely low incidence of hypoglycemia 2.
- SGLT-2 inhibitors and GLP-1RAs have been shown to have beneficial effects on mortality and major cardiovascular adverse events (MACE) compared to DPP-4 inhibitors and sulphonylureas, and are recommended as add-on therapy to metformin in patients with T2D and high risk for cardiovascular disease 4.
- Pioglitazone add-on therapy has been shown to significantly reduce HbA1c levels, fasting blood glucose, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) in patients with T2DM inadequately controlled with metformin and Dapagliflozin 5.
Treatment Options
- Metformin: first-line oral therapy for T2DM 3
- Pioglitazone: can be administered in combination with metformin, sulfonylureas, exenatide, DPP-4 inhibitors, or insulin 2
- SGLT-2 inhibitors: recommended as add-on therapy to metformin in patients with T2D and high risk for cardiovascular disease 4
- GLP-1RAs: recommended as add-on therapy to metformin in patients with T2D and high risk for cardiovascular disease 4
- DPP-4 inhibitors: can be used as add-on therapy to metformin, but have limited benefits compared to SGLT-2 inhibitors and GLP-1RAs 4
- Sulphonylureas: can be used as add-on therapy to metformin, but have limited benefits compared to SGLT-2 inhibitors and GLP-1RAs 4