A major new study has taken a close look at how different medications work alongside metformin—the go-to first-line treatment for people with type 2 diabetes.
Known as the GRADE study (short for Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study), the research followed over 5,000 people with type 2 diabetes to figure out which medication combinations helped manage blood sugar levels the best over a long period.
The participants were all already taking metformin, which is widely prescribed as the starting point for diabetes treatment.
To test what works best as a second medication, researchers randomly assigned each person to add one of four options: sitagliptin, liraglutide, glimepiride, or insulin glargine.
For four years, researchers tracked how well these different combinations helped people keep their blood sugar in the healthy target range. Blood sugar control is essential in diabetes because poor management over time can lead to serious health problems like heart disease, kidney damage, and vision loss.
The results were clear: the combinations of metformin with liraglutide and metformin with insulin glargine did a better job at keeping blood sugar under control than the other two options. This held true regardless of a person’s age, gender, race, or background, which means these two combinations could be beneficial for many different people with type 2 diabetes.
But even the best-performing combinations didn’t guarantee perfect blood sugar control. In fact, around 75% of all participants struggled to maintain their target levels over the full four years of the study.
This highlights how difficult it can be to manage type 2 diabetes in the long run and shows that medicine alone isn’t always enough. Factors like lifestyle changes, regular exercise, diet, and mental well-being also play huge roles.
One especially interesting finding was that the group taking liraglutide had fewer heart-related complications, a major concern for people with diabetes. This could mean that liraglutide has added benefits beyond just lowering blood sugar, which makes it a particularly promising option for people with diabetes who are also at risk of heart disease.
Published in The New England Journal of Medicine by Dr. Henry Burch and his team, the study doesn’t just compare medication effectiveness—it also opens a bigger conversation about the challenges of diabetes care.
It shows how even with good treatment plans, many people still struggle to stay within healthy ranges, pointing to a need for more support, better tools, and new innovations.
This research offers helpful direction for doctors and patients, showing that combining metformin with liraglutide or insulin glargine may be more effective for many people.
However, the study also makes it clear that there is no one-size-fits-all answer in diabetes care. Personalized treatment—based on a patient’s unique health history, lifestyle, and risk factors—is more important than ever.
This study is one of the largest and most detailed comparisons of diabetes drug combinations so far, and it adds a great deal to what we know. The key takeaway is that while certain drug pairings—especially metformin with liraglutide or insulin glargine—are more effective, managing type 2 diabetes is still a long-term challenge for most patients.
With three out of four participants unable to maintain their target blood sugar over four years, it’s clear that we need more than just good medications. This includes better education, more personalized treatment strategies, and continued research to explore new therapies that are easier to manage and provide longer-lasting results.
The findings also highlight the potential for medications like liraglutide to do more than just lower blood sugar—possibly protecting the heart as well. For healthcare providers, this study provides strong evidence to guide more effective treatment decisions, but also serves as a reminder that the journey toward long-term diabetes control is complex and ongoing.
If you care about diabetes, please read studies about diabetes and vitamin B12, and the right diet for people with type 2 diabetes.
For more health information, please see recent studies about how to eat smart with diabetes, and turmeric and vitamin D: a duo for blood pressure control in diabetic patients.
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