SGLT2 Inhibitors: 4 Points on Efficacy, Safety You Need to Know

August 19, 2014

Studies looking at add-on treatment with SGLT2 inhibitors show their effects on glycemic control to be roughly additive. Here, a concise look at clinical trial results plus guidance on renal dose adjustment.

The insulin-independent action of the SGLT2 inhibitors makes their use appropriate at most points in the disease progression of T2DM. In clinical trials they have also been shown effective as add-on therapy in patients not achieving A1C goals on monotherapy or dual therapy with existing agents.The slides above summarize the results of the key "combination" studies, provide guidance on dosage adjustment for renal impairment, Â and review the primary pros and cons currently known about SGLT2 inhibitors.For the part 1 slide show, "SGLT2 Inhibitors: 5 Things You Should Know," click here.

Canagliflozin, when added to metformin and pioglitazone lowered A1C more effectively than placebo. When added to metformin and compared with glimepiride, canagliflozin at low dose was non-inferior to glimeperide and at high dose was more effective. For more information on the pioglitazone study, click here., .

Dapagliflozin when added to metformin was as effective as DPP-4 inhibitors, thiazolidinediones, sulphonylureas, and GLP-1 antagonists. Added to insulin, dapagliflozin decreased A1C vs placebo and avoided the need to raise insulin dose. ,

Empagliflozin was more effective in lowering A1C than glimepiride when added to metformin; when added to insulin and metformin in patients with type 2 diabetes who were obese and had poorly controlled disease, empagliflozin improved glycemic control and reduced weight without increasing the risk of hypoglycemia and with lower insulin requirements. For more information on the glimepiride study, click here., .

Dosing of SGLT2 inhibitors must be based on kidney function. The drugs were studied using estimated glomerular filtration rate versus estimated creatinine clearance with the Cockgroft-Gault equation. Also, there are higher renal dosing cut-offs. Dosing in the elderly must be approached with caution. See professional prescribing information for additional details on dosing for renal insufficiency: , .

SGLT2 inhibitors induce glycosuria, improve glycemia, reduce A1C levels, have low risk of hypoglycemia, and modestly reduce weight and blood pressure. As add-on therapy, could improve glycemic control and help stabilize insulin dosage.

SGLT2 inhibitors increase the risk of genital mycotic infections, polyuria, and volume depletion, and may increase the risk of ischemic stroke, especially early in treatment.

The FDA requires post-marketing studies and pharmacovigilance programs of all 3 manufacturers of approved SGLT2 inhibitors. Primary concerns center on cardiovascular outcomes, risk for bladder cancer, pediatric safety, and animal toxicity studies focused on renal development.