Metformin has become the standard first-line therapy for diabetes patients with low cardiovascular risk. But several other diabetes medications are out there, which makes you wonder if it might be a good idea to use one or more of them in addition to, or in place of, metformin.
In a study just published in the Annals of Internal Medicine, a team of researchers led by Apostolos Tsapas, MD, PhD, Associate Professor of Medicine at Aristotle University Thessaloniki in Greece, reported on the outcome of their research into just that question.
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The researchers surveyed the results of more than 450 trials of 21 diabetes medications from nine classes of drugs used in adults with type 2 diabetes. Their hope was that by scrutinizing the most current and thorough studies, their report could serve as a “bridge” between basic scientific research and the way in which medicine is practiced in the doctor’s office.
The researchers established certain criteria for the studies they included in their investigation. The studies had to have been at least 24 weeks long and they had to have examined the effects of blood-sugar-lowering drugs on death rates, on blood sugar control and on cardiovascular disease.
The researchers’ basic conclusion was that metformin should remain the foundation of initial therapy for patients with diabetes and that, in terms of cardiovascular outcomes, there is no benefit to adding other agents for patients with low cardiovascular risk. As they put it, “The use of metformin as first-line treatment of drug-naïve patients at low cardiovascular risk seems justified.” (“Drug-naïve” means not having previously taken a medication.)
However, the researchers also reported more detailed findings. For example, in patients already using metformin, semaglutide injections (brand name Ozempic) were better at lowering HbA1c (a measure of glucose control over the previous two to three months) levels than other treatments. For patients with heightened cardiovascular risk, oral semaglutide (brand name Rybelsus), empagliflozin (Jardiance), liraglutide (Victoza), dapagliflozin (Farxiga), and extended-release exenatide (Bydureon) reduced mortality from all causes in patients with higher cardiovascular risk who were already taking metformin. Oral semaglutide, empagliflozin or liraglutide also lowered cardiovascular death. The chances of stroke were lower both with semaglutide injections plus metformin and with dulaglutide (Trulicity) plus metformin. As for SGLT-2 inhibitors (canagliflozin [Invokana], dapagliflozin or empagliflozin), which are fairly new medications that lower glucose independent of insulin, the researchers reported that, when used along with metformin, they lowered the risk of end-stage kidney disease and of hospitalization for heart failure. But they also pointed out that each SGLT-2 inhibitor carries its own risk, such as lower-limb amputation and diabetic ketoacidosis, a serious problem that happens when the body breaks down fat too quickly.
The authors of the new paper decided they were unable to draw a conclusion about the “optimal” treatment for drug-naïve patients who are at high cardiovascular risk. But they were able to say that whatever glucose-lowering treatment is used, it should be tailored to the individual patient’s needs and risk factors, although the foundation of treatment should remain metformin, advice that’s consistent with the guidelines of the American Diabetes Association.