First head-to-head study reveals greater benefits of SGLT2 inhibitors for cardiovascular events in type 2 diabetes

Pharma News: A new Australian study has compared two classes of type 2 diabetes drugs and found that one of the two classes is associated with a greater reduction of major adverse cardiovascular events in men than in women.

The two classes of drugs are SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP-1RA). Both classes of medication reduce major adverse cardiovascular events in people with type 2 diabetes. SGLT2 inhibitors include AstraZeneca’s Forxiga (dapagliflozin), Novartis’ Entresto (sacubitril-valsartan) and Eli Lilly and Boehringer Ingelheim’s Jardiance (empagliflozin).

Despite women with type 2 diabetes having a higher risk of developing cardiovascular disease and heart failure than men with type 2 diabetes, treatment approaches for diabetes-induced cardiovascular disease remain the same across the sexes.

As such, Monash Institute of Pharmaceutical Sciences (MIPS) researchers set out to directly compare and report the sex-specific effects of SGLT2i with GLP-1RAs on major adverse cardiovascular events in men and women, with further subgroup analyses based on age and heart failure history.

The study included 8,026 Australian men and women with type 2 diabetes (≥30 years) who were dispensed SGLT2i or GLP-1RA class of medicines within 60 days of discharge from the hospital.

In a median follow-up period of over 2 years, exposure to SGLT2i reduced the risk of major adverse cardiovascular events, such as heart failure and stroke, to a greater extent in men of all ages with type 2 diabetes than women in the same age cohort.

Overall, men dispensed SGLT2i had a 22% reduction rate in major adverse cardiovascular events compared to men supplied a GLP-1RA, whilst in women there was no significant difference between SGLT2i and GLP-1RAs for their effects on major adverse cardiovascular events.

The researchers demonstrated for the first time that SGLT2i, when directly compared to GLP-1RAs, more favourably reduce major adverse cardiovascular events rates in both older men and women with T2D, in men with baseline heart failure, and in women with baseline atherosclerotic CVD.

The study’s first author, Abhipree Sharma, said the apparent disparity between the relative benefits of SGLT2i versus GLP-1RAs in type 2 diabetes men and women warrants further investigation.

“Treatment recommendations for type 2 diabetes-associated cardiovascular disease and heart failure remain the same in men and women despite known sex differences in the development and presentation of these diseases. Our analyses suggest that these newer classes of glucose-lowering therapies can in fact exert more favourable effects depending on age and sex, which is something we believe needs to be explored further,” said Ms Sharma.

Leader of Heart Failure Pharmacology at MIPS and corresponding senior author, Professor Rebecca Ritchie, said there may be a number of reasons women with type 2 diabetes are more at risk of developing cardiovascular disease and heart failure than men with type 2 diabetes.

“Typically women with type 2 diabetes present with greater insulin resistance, endothelial dysfunction, inflammation, abdominal adiposity, body mass index, and blood glucose and cholesterol levels than men with type 2 diabetes. Additionally, increases in cardiovascular disease and heart failure risk in postmenopausal women suggests an integral role for estrogen in cardioprotection in women,” said Professor Ritchie.

“Our hope is that the findings from this large population-based study will lead to a deeper dive into the most effective pharmacological treatment recommendations based on factors including sex, age and heart failure history,” Professor Ritchie concluded.

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