Silvio E. Inzucchi
PHILADELPHIA — The role metformin should play as first-line therapy in patients with type 2 diabetes and cardiovascular disease continues to spark debate, a discussion at the Heart in Diabetes Clinical Education Conference indicated.
Silvio E. Inzucchi, MD, medical director of the Diabetes Center at Yale-New Haven Hospital in Connecticut argued that metformin should remain the first-line treatment in these patients.
“This position is well-deserved and is based on its efficacy, safety, weight neutrality, likely cardiovascular benefits and low costs. While data regarding SGLT2 and GLP-1 receptor agonists are certainly exciting, most of those patients in those cardiovascular outcome trials were already on metformin at baseline,” he said.
“In admittedly small randomized trials, we do see a consistent benefit on major adverse CV events. Some studies have also shown benefits in two groups of patients previously felt to have contraindications for metformin therapy — heart failure and mild-moderate chronic kidney disease,” Inzucchi told Endocrine Today.
Inzucchi also noted the agent’s unparalleled popularity in various combination regimens and its consistent appearance in the American Diabetes Association guidelines for more than a decade as “foundation therapy” to support his claim. He called for studies with the newer agents vs. metformin in such patients to unseat the latter in its position as optimal initial glucose-lowering therapy.
Vivian Fonesca, MD,
FRCP, endocrinology section chief at Tulane University of Health Sciences in New Orleans, argued against metformin’s status as first-line treatment in patients with type 2 diabetes, partly because of the limitations of the data Inzucchi presented.
“People with kidney disease were not included in the UKPDS or any one of a number of other trials. [Gastrointestinal] side effects are very common, there is also risk for B-12 deficiency ... it has no effect on beta-cell function, modest weight loss, a cardiovascular benefit that is no better than insulin, no microvascular benefit at all, and worsens neuropathy and cognition," Fonseca argued.
Fonesca also suggested that if metformin came up for FDA approval now, 20 years after it was first approved, it might not pass all of the agency’s standards.
“What would happen if you compared metformin to usual care? Would it reduce [myocardial infacrtion], mortality, renal disease progression, lead to worsening microvascular complications and would you have a high study drop out due to diarrhea or inertia?” Fonseca asked.
The answer to most of those questions would not bode well for metformin’s approval today, he said.
The ADA previously stated it would update the online version of its Standards of Care as needed when new evidence warrants immediate clinical implementation and currently recommends metformin, “if not contraindicated and if tolerated, [as] the preferred initial pharmacologic agent for the treatment of type 2 diabetes.” – by Janel Miller
Inzucchi SE, Fonesca V. Metformin is still the best initial therapy for T2DM with CVD. Presented at: Heart in Diabetes Clinical Education Conference; July 13-15, 2018; Philadelphia.
Disclosures: Fonesca reports he receives consulting fees from Astra-Zeneca, Eli Lilly, Novo Nordisk, Sanofi-Aventis and Takeda, and he has clinical trial leadership roles with Asahi, BRAVO4Health, Mellitus Health, Microbiome Technologies, Novo Nordisk, Sanofi-Aventis and Takeda. Inzucchi reports he has served on research steering committees for AstraZeneca, Boehringer Ingelheim, Eisai (TIMI), Novo Nordisk and Sanofi/Lexicon, as a consultant and advisor to vTv Pharmaceuticals and on a data monitoring committee for Intarcia.