Update on developments with SGLT2 inhibitors in the management of type 2 diabetes

Abstract

The importance of the kidney’s role in glucose homeostasis has gained wider understanding in recent years. Consequently, the development of a new pharmacological class of anti-diabetes agents targeting the kidney has provided new treatment options for the management of type 2 diabetes mellitus (T2DM). Sodium glucose co-transporter type 2 (SGLT2) inhibitors, such as dapagliflozin, canagliflozin, and empagliflozin, decrease renal glucose reabsorption, which results in enhanced urinary glucose excretion and subsequent reductions in plasma glucose and glycosylated hemoglobin concentrations. Modest reductions in body weight and blood pressure have also been observed following treatment with SGLT2 inhibitors. SGLT2 inhibitors appear to be generally well tolerated, and have been used safely when given as monotherapy or in combination with other oral anti-diabetes agents and insulin. The risk of hypoglycemia is low with SGLT2 inhibitors. Typical adverse events appear to be related to the presence of glucose in the urine, namely genital mycotic infection and lower urinary tract infection, and are more often observed in women than in men. Data from long-term safety studies with SGLT2 inhibitors and from head-to-head SGLT2 inhibitor comparator studies are needed to fully determine their benefit–risk profile, and to identify any differences between individual agents. However, given current safety and efficacy data, SGLT2 inhibitors may present an attractive option for T2DM patients who are failing with metformin monotherapy, especially if weight is part of the underlying treatment consideration.

Keywords:

• anti-diabetes agents
• efficacy
• hyperglycemia
• safety
• sodium glucose co-transporter type 2 inhibitors
• type 2 diabetes mellitus

Acknowledgments

Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Debra Brocksmith, MB ChB, PhD, of Envision Scientific Solutions during the preparation of this manuscript. Boehringer Ingelheim was given the opportunity to check the data used in the manuscript for factual accuracy only.

Author contributions

The author was fully responsible for all content and editorial decisions, was involved at all stages of manuscript development, and has approved the final version of the manuscript that reflects the author’s interpretation and conclusions.

Disclosure

The author has received research grants to his institution from Berlin-Chemie/Menarini, Eli Lilly, Merck Sharp and Dohme, Novartis, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Lilly Deutschland, MetaCure, Roche Pharma, Novo Nordisk, and Tolerx for participation in multicenter clinical trials. He has received consulting fees and/or honoraria for membership in advisory boards and/or honoraria for speaking from Amylin, AstraZeneca, Berlin-Chemie/Menarini, Boehringer Ingelheim, Bristol-Myers Squibb, Diartis Pharmaceuticals, Eli Lilly, Hoffmann-LaRoche, GlaxoSmithKline, Intarcia Therapeutics, MannKind, Merck Sharp and Dohme, Novartis, Novo Nordisk, Sanofi, Takeda, Versartis, and Wyeth Research, including reimbursement for travel expenses.

Supplementary material

Table S1 SGLT2 inhibitor clinical trials (Phase 11+)

Table S2 SGLT2 and SGLTI inhibitors currently in the development pipeline

Table S3 Efficacy data from pivotal clinical trials of SGLT2 inhibitorsa

Table S4 Safety data from pivotal clinical trials of SGLT2 inhibitorsa

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