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Journalism of Courage
US pharmaceutical giant Eli Lilly’s weight-loss drug tirzepatide was found to be more effective in preventing heart attacks and strokes compared to its previous GLP-1 medication dulaglutide. The preliminary results from a yet-to-be published large trial showed that the risk of a major adverse cardiovascular event was eight per cent lower in people who were put on the new therapy. Tirzepatide is sold under the brand name Mounjaro.
Belonging to a group of medicines called incretin mimetics — which mimic hormones that play a key role in regulating insulin levels, blood sugar levels and appetite — both the medicines were initially approved for the treatment of diabetes, with tirzepatide later receiving approval for the treatment of obesity and other related conditions such as obstructive sleep apnea. Dulaglutide mimics the action of the GLP1 hormone while tirzepatide mimics the combined action of GLP1 and GIP hormones.
The trial found an eight per cent lower risk of major adverse cardiovascular events such as cardiovascular deaths, heart attacks and strokes in people who were on tirzepatide as compared to those on dulaglutide. Tirzepatide was found to reduce the risk of such events by 28 per cent against a placebo, by comparing the results of the current trial with a 2019 trial of dulaglutide against placebo.
Another important finding of the trial was a 16 per cent lower risk of all-cause mortality in people who were on tirzepatide, compared to those on dulaglutide. The company said that the medicine reduced the risk of all-cause mortality by 39 per cent against placebo — again by comparing data from the current trial with the 2019 dulaglutide trial.
The current trial also demonstrated that tirzepatide was better at slowing the decline of kidney function in participants who were at a high risk of chronic kidney disease. Tirzepatide slowed the decline in the kidney’s filtration rate by 3.54 mL/min/1.73 m2 as compared to dulaglutide.
The trial also showed that tirzepatide was more effective at reducing three-month average blood glucose levels as well as weight when compared to dulaglutide. The use of tirzepatide led to a 1.73 per cent reduction in HbA1c levels at 36 months as compared to 0.9 per cent with dulaglutide use. The participants on tirzepatide dropped 12 per cent of their body weight during the trial period as compared to 4.95 per cent with dulaglutide.
With the new generation weight-loss drugs gaining popularity across the globe, it is essential for these drugs to demonstrate protection against heart diseases, especially since it is a common comorbidity along with obesity and diabetes.
While there is a link between uncontrolled blood glucose levels and heart disease, not all diabetes medicines protect the heart. In fact, a previous class of diabetes medicines called glitazones were found to increase the risk of heart failure. With the end-game of these medicines being saving lives — and not just controlling blood glucose levels or body weight — the US Food and Drug Administration now requires the medicines to demonstrate that they do not harm the heart or, better yet, they offer protection against cardiovascular events.
The new classes of diabetes medicines such as GLP-1 and SGLT-2 were found to protect the heart as well. Importantly, the competitor of Eli Lilly’s tirzepatide — Novo Nordisk’s semaglutide — has FDA approval as treatment for reducing risk of heart diseases.
These medicines work by improving the secretion of insulin, which helps in removing glucose from the blood to the cells for use as energy. They inhibit the secretion of the hormone glucagon that stimulates the liver to release stored glucose into the bloodstream, slow down the emptying of the stomach so that the blood glucose levels do not spike suddenly and reduce appetite by signalling to the brain that you are full.
The drugs have become popular owing to their weight-loss properties, which at times can be as effective as bariatric surgery.
