Pharmacological treatment of T2D

Treatment TypeAgent
Initial Pharmacological treatment

Practice pearl: When starting Sulphonylureas (SU) teach patient how to prevent, recognize and treat hypoglycemia.
Metformin. Titration from 500 to 2000 mg per day. Reduce dose to 1000 mg per day when renal function is in stage 3A and contraindicated when renal function is in stage 3B or above.

Definitive metformin intolerance or when it is contraindicated, some guidelines recommend SU, alpha-glucosidase inhibitors or dipeptidyl peptidase-4 (DPP-4) inhibitors as the first option, but some guidelines, such as the American Association of Clinical Endocrinologists, recommend glucagon-like peptide-1 (GLP-1) receptor agonists or sodium-glucose cotransporter-2 (SGLT-2) inhibitors should be the first options. Glibenclamide/glyburide is not recommended as it is associated with the greatest risk of hypoglycemia
Initial combination therapy 

Practice pearl: Use fixed-dose combinations to increase adherence
Consider combination treatment when the baseline HbA1c is 1% to 2% points above target. Metformin plus another glucose lowering drug SU (except glibenclamide/glyburide), a DPP-4 inhibitor or an SGLT-2 inhibitor may be the preferred option.
Initial Insulin therapyWhen indicated (e.g. very high blood glucose level, symptoms and signs of acute decompensation) most guidelines recommend insulin alone or in combination with other GLDs. 

Start with basal insulin 10 unit or 0.2 units/kg, titrate once or twice weekly at 1 to 2 units each time to achieve a target fasting blood glucose between 3.9 and 7.2 mmol/L (70 and 130 mg/dL).
Patient must learn how to self-monitor blood glucose and how to recognize and treat hypoglycemia
Add-on Therapy when monotherapy is not enough to control blood glucose
Avoid waiting longer than 3 to 6 months when HbA1c is above target before adding a second GLD. Consider patient’s profile (age, body weight, complications and duration of disease) when choosing the best GLD to add.
Dual therapyThe best choices of add-on to metformin are SUs (except glibenclamide/glyburide), DPP-4 inhibitors, SGLT-2 inhibitors, or alpha-glucosidase inhibitor. A GLP-1 receptor agonist may be considered if weight loss is part of treatment goal.
Triple therapyA third GLD should be added if dual therapy with metformin does not achieve the HbA1c target.
The most common choice to add to two oral GLDs is basal insulin. GLP-1 receptor agonist can be added instead if weight loss has been insufficient.

Triple therapy with three oral GLDs may be effective before adding an injectable. The usual triple combinations are metformin + SU + pioglitazone or metformin + SU + DPP-4 inhibitor, but recently SGLT-2 inhibitors have been considered as an option to add to metformin + SU or metformin + DPP-4 inhibitor. Metformin + SGLT-2 inhibitor + GLP-1 receptor agonist may be a useful combination for those who have not lost sufficient weight.