When metformin is not enough: Pros and cons of SGLT2 and DPP‐4 inhibitors as a second line therapy

Abstract

The newer oral therapies for type 2 diabetes mellitus, dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium glucose cotransporter 2 (SGLT2) inhibitors, have advantages over older agents. Dipeptidyl peptidase-4 inhibitors are weight neutral and have few adverse effects. Sodium glucose cotransporter 2 inhibitors have additional benefits: weight loss, blood pressure reduction, cardiovascular risk reduction, and renoprotective effects. Sodium glucose cotransporter 2 inhibitors have increased risk of urogenital infections and possible risk of "euglycaemic" diabetic ketoacidosis. It is important to balance the benefits over the older-oral therapies as these agents are more expensive; yet some analyses suggest that they are within the limits of what is considered cost-effective in health care. We discuss the relative merits and drawbacks of these 2 classes and consider their roles in the treatment of type 2 diabetes mellitus. We suggest a number of patient profiles where early use of these agents could be used. We favour the use of SGLT2 inhibitors over DPP-4 inhibitors as add on therapy to metformin when glycaemic targets have not been achieved given their similar glycaemic efficacy and the additional benefits of SGLT2 inhibitors. We particularly favour SGLT2 inhibitors in those where additional weight loss and blood pressure reductions are desired, and in patients with heart failure or cardiovascular disease. Care should be taken to warn patients about genital fungal infections and to avoid use in people with risk factors for SGLT2 associated ketoacidosis. We favour DPP-4 inhibitors in those where side effects of other agents are of concern, the frail elderly population, and those with renal disease precluding SGTL2 inhibitor use.

Rationale for Timely Insulin Therapy in Type 2 Diabetes Within the Framework of Individualised Treatment: 2020 Update

“…DDP4 or SGLT2 inhibitors) [ 12 ]. Avogaro et al [ 52 ] showed in a meta-analysis of DPP4 inhibitors an apparently accepted mean increase in HbA 1c of 0.22% after 52 weeks of usage. Long-term loss of glycaemic control of 0.30% over 4 years of treatment was observed with dapagliflozin [ 53 ].…”

Meta‐analysis on the efficacy and safety of SGLT2 inhibitors and incretin based agents combination therapy vs. SGLT2i alone or add‐on to metformin in type 2 diabetes

“…Considering their complementary physiological pathways, the combination of incretin‐based agents may prevent the rise in EGP and thus improve the hypoglycemic efficacy. Recent studies have confirmed a favourable role of these new classes of oral therapies over the conventional hypoglycemic agents in the treatment of T2DM and suggested a pleiotropic benefit when they were used in combination . What is more, each drug class has specific adverse effect (AE) profiles, and their combination has the potential to change respective side effect profiles or to mitigate or cause additive AEs, which still remains unclear.…”

Pharmacologic strategies to reduce cardiovascular disease in type 2 diabetes mellitus: focus on SGLT‐2 inhibitors and GLP‐1 receptor agonists

“…Importantly, GLP‐1RAs and SGLT‐2 inhibitors have a different adverse event profile . Most of these events are infrequent, but yet they were significantly greater in the treatment groups compared to the placebo ones.…”