According to the study, 2 common drugs outperform others

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One study found that the common diabetes drugs glargine and liraglutide are the most effective at lowering blood glucose levels. MJ_Prototype/Getty Images
  • Researchers compared the effectiveness of four diabetes drugs in lowering blood glucose levels.
  • They found that glargine and liraglutide are more effective at lowering blood glucose levels. However, liraglutide and sitagliptin induced the greatest weight loss.
  • They said their findings could help health professionals prescribe different drugs to patients based on their needs.

According to the American Diabetes Association, about 11.3% of the U.S. population, or 37.3 million people, had diabetes in 2019. Of those people, 35.4 million had type 2 diabetes .

Type 2 diabetes occurs when the body does not produce enough insulin or becomes resistant to insulin and therefore cannot easily absorb glucose from the blood.

Researchers and health professionals generally agree that metformin, an antidiabetic drug used to lower blood sugar levels and increase insulin sensitivity, along with exercise and diet, is the best strategy for the early care of diabetes. However, the later stages of diabetes require other medications along with metformin.

Currently, there is no consensus on which drug is most effective in lowering blood glucose levels. Research comparing the effectiveness of antidiabetic medications could thus improve patient care.

Researchers recently conducted a clinical trial to evaluate the effectiveness of metformin along with four commonly prescribed antidiabetic drugs.

They found that drugs known as insulin glargine and liraglutide were most effective at keeping blood glucose levels within the recommended range.

The results were published in two papers in the New England Journal of Medicineone discussing blood glucose findings and the other on cardiovascular outcomes.

For the study, researchers followed 5,047 people who had received metformin for type 2 diabetes for an average of 5 years. They had an average age of 57, with more than 60% identifying as white men; all had type 2 diabetes for less than 10 years at the start of the study.

The researchers randomly assigned participants to one of four glucose-lowering medications:

  • insulin glargine U-100
  • glimepiride
  • liraglutide
  • sitagliptin

The researchers controlled the participants glycated hemoglobin, which measures your average blood glucose levels over the previous 2-3 months. They also looked at cardiovascular outcomes, including hypertension and cholesterol.

Experts usually advise people with type 2 diabetes to have glycated hemoglobin below 7% to minimize the negative health impacts of their diabetes. The study reported that 71% of participants had glycated hemoglobin of 7% or higher at some point during the five years of follow-up.

The same was true for the 60% of participants with the lowest blood glucose levels, from 6.8% to 7.2%, at the start of the study.

The researchers, however, wrote that average blood glucose levels decreased during the trial by about 0.3% compared to the start of the study.

They also noted that although the drug combinations generally had similar effects on glycated hemoglobin levels, glargine and liraglutide maintained target levels for six months longer than those using the less effective drug, the sitagliptin

Glargine was more effective in maintaining blood glucose control; only 39% of participants had glycated hemoglobin levels above 7.5%. Meanwhile, sitagliptin was the least effective at maintaining blood glucose levels.

The researchers also recorded some side effects. For example, those taking liraglutide and sitagliptin lost an average of 3.5 kg and 2 kg during the study period, while those using other medications had a relatively stable weight.

Although all the drugs had “acceptable safety profiles,” they noted that those taking liraglutide were more likely to report gastrointestinal side effects.

Glimepiride, followed by glargine, was linked to the highest incidence of hypoglycemia, when blood sugar levels are below the standard range. They noted, however, that cases were rare.

The researchers noted that most participants had hypertension (77%) or dyslipidemia (96%) at baseline. More than 60% of participants who did not have hypertension and more than 90% who did not have dyslipidemia before the study developed the conditions at the end.

The results suggest that there are no material differences in the rates of hypertension or dyslipidemia between the four drugs at the end of the study. There were small differences in rates of cardiovascular disease, with liraglutide use associated with a slightly lower risk of developing any cardiovascular disease than use of the other drugs.

“We don’t know exactly how cardiovascular risk is reduced, but it’s probably not because of lowering glucose. In fact, heart disease risk starts in the pre-diabetes range,” said Dr. Heather Ferris, Ph. D., an assistant professor and endocrinologist at the University of Virginia’s UVA Health Academic Health System, who is not involved in the study.

“It is worth noting that the glargine and glimepiride groups lost less weight during the intervention and were more likely to develop hypertension (probably weight-related). This is an important cardiac risk factor and may explain much of the difference in outcomes,” added Dr. Ferris.

“While I don’t think any of the findings in this study were particularly surprising, this study allows providers to see direct comparisons of different agents for the first time. It confirmed the many known pros and cons of the drugs,” said Dr. ferries

“Further away, [the study] suggests that liraglutide, which has been shown to be beneficial for cardiovascular risk in a high-risk population, likely provides benefit to a lower-risk group of people with diabetes,” he added.

“This study was designed to provide [healthcare] providers with important information on how to guide the long-term management of type 2 diabetes,” he said Dr. Henry Burchprogram director at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), one of the study’s authors.

“This is an integral step towards precision medicine for diabetes care, as these results can now be used in the decision-making process for each individual patient in light of their levels of diabetes control. glucose, how the medication is tolerated, and the person’s other health considerations,” added Dr. Burch.

The researchers concluded that glargine and liraglutide, when added to metformin, are modestly more effective than other drugs in achieving and maintaining average blood glucose levels in the target range.

The researchers wrote that their results are limited because they compared only four of many glucose-lowering medications.

Dr. Ferris added: “Although patients were randomly assigned to the four treatment groups, I think it’s important to emphasize that in the real world, patients’ risks of hypoglycemia, weight gain, and cardiovascular disease are be careful when prioritizing medicines for a given individual”.

“This study does not prioritize which drug to use for everyone. Rather, it shows some small differences between the agents in both benefits and risks that may help doctors prioritize for a given individual,” he noted.

“It is also worth noting that there were some patients in this trial with well-controlled diabetes. In general, intensification of therapy in this group would not be recommended unless it was with an agent such as liraglutide or an SGLT2 inhibitor (not tested in this study), which can be initiated for cardiac or renal benefits,” he concluded.

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