Two popular diabetes drugs outperform others in large clinical trial

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Researchers compared four drugs used to treat type-2 diabetes in a large clinical trial. They found that insulin glargine and lipaglitide performed better than the other four drugs. This is because they were approved by the U.S. Food and Drug Administration for maintaining blood glucose levels within the recommended range. Blood glucose management is an important component of keeping people living with type 2 diabetes well. All four medications were combined with metformin, the first-line drug for type 2 diabetes treatment.

Nearly 37 million Americans suffer from diabetes. Around 90 to 95% of these people have type 2 diabetes. Diabetes sufferers who maintain their blood glucose levels within a normal range are at a lower risk of developing complications like nerve, kidney and eye disease. Type 2 diabetes requires multiple medications to control blood sugar levels.

Although there is general agreement among doctors and health care professionals that metformin with diet and exercise is the best way to manage diabetes early, there is not consensus on what next to keep high blood sugar under control.

The Glycemia Reduction Strategies in Diabetes: A Comparative Effects (GRADE) study was launched in 2013. It was conducted at 36 U.S. research centers. It was designed to compare four of the major drugs approved by FDA at the time GRADE began to treat diabetes with metformin. Two papers published major results in this study. The New England Journal of Medicine.

“This study was created to provide important information to health care providers on how to guide long-term type 2 diabetes management,” stated Dr. Henry Burch of NIDDK, GRADE’s project scientist. “This is an important step towards precision medicine for diabetes care. These results can now help in the decision-making process of each individual patient in light their levels of glucose control, how well they tolerate the medications, and any other health considerations.

The study included 5,047 type 2 diabetics from different racial/ethnic backgrounds who were already taking metformin. Randomly, participants were assigned to one of four treatment programs. Three groups received metformin plus a medicine to increase insulin levels, sitagliptin or liraglutide. The fourth group received metformin plus insulin glargine U-100 (a long-acting insulin).

The study showed that participants who took metformin plus insulin glargine or liraglutide had an average of four years of follow up. This was compared to sitagliptin and glimepiride. This translated to approximately six months more time with blood glucose levels within the target range, compared to sitagliptin (which was the least effective in maintaining target levels). The treatment effects did not differ by gender, age, race, ethnicity, or sexual orientation.

None of the combinations outperformed the other. Despite a decrease in blood sugar levels during the study, almost three quarters of participants were unable maintain the blood glucose target for four years. This highlights the difficulty in maintaining the recommended targets in type 2 diabetes patients.

GRADE effectively shows which drugs are most effective at meeting and maintaining blood glucose targets over time. However, we need to develop even more effective strategies to maintain acceptable glucose levels for long-term periods,” said Dr. David M. Nathan (Grade Study Chair), director of the Massachusetts General Hospital Diabetes Center. “We still have much to do, including evaluating other treatments and combinations to help type 2 diabetics achieve long-term glucose control.

The effects of diabetes-related cardiovascular diseases on the treatment outcomes was also studied. Researchers found that participants in liraglutide were less likely to develop any cardiovascular disease than those in other groups.

Side effects of the drugs were also studied in the study.

  • Although severe hypoglycemia (often called a low-blood glucose reaction) was rare, it affected more participants who were prescribed glimepiride (2.2%).
  • Gastrointestinal symptoms were more common when liraglutide was used than the other three treatment options.

Participants in all treatment programs lost an average of 7 and 4 pounds, respectively. Over the course of four years, participants in sitagliptin or liraglutide arms lost more (on average, 7 and 4 lbs, respectively) than those in glimepiride and glargine arms (which were less than 2 lbs).

Dr. Griffin P. Rodgers, Director of NIDDK, stated that there are many options for type 2 diabetes treatment. This can make it difficult for patients and health care providers to decide which drug is best. “NIDDK is uniquely positioned in support of comparative effectiveness trials such as GRADE to help doctors make evidence-based recommendations that will lead to better health for their patients and all people living with type 2.

At the launch of GRADE Recruitment, the FDA did not approve SGLT2 inhibitions, a now-available type for diabetes drugs. The FDA did not approve it and it was not included in this study.

Two medications are most effective in lowering blood sugar levels in type 2 diabetics patients, according to trial results

More information:
New England Journal of Medicine (2022). www.nejm.org/doi/full/10.1056/NEJMoa2200433

Provided by
National Institute of Diabetes and Digestive and Kidney Diseases

Two diabetes drugs that are well-known outperform the rest in large clinical trials (2022 and September 21).
Retrieved 22 September 2022
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