Type 2 diabetes affects the way the body controls sugar in the blood. Over time, high blood sugar can damage blood vessels and organs, increasing the risk of heart disease, kidney problems, nerve damage and vision loss.
Metformin is usually one of the first medicines prescribed to people with type 2 diabetes. However, diabetes often changes over time, and many people eventually need another medicine to keep their blood sugar within a healthy range.
A large U.S. study called GRADE compared four commonly used medicines that can be added to metformin. Researchers wanted to learn which treatment could keep blood sugar under control for the longest time.
The study included 5,047 adults with type 2 diabetes from different racial and ethnic backgrounds. Everyone was already taking metformin when they entered the study, and participants were randomly assigned to receive one of four additional treatments.
The four treatments were sitagliptin, liraglutide, glimepiride and insulin glargine U-100. These medicines lower blood sugar in different ways, giving researchers a chance to directly compare several widely used approaches.
Glimepiride helps the pancreas release more insulin, while sitagliptin works through hormones involved in controlling blood sugar after meals. Liraglutide belongs to a group of medicines called GLP-1 receptor agonists and helps the body release insulin when needed, while also affecting appetite and digestion.
Insulin glargine is a long-acting form of insulin. It provides a steady supply of insulin over many hours and helps move glucose from the blood into cells, where it can be used for energy.
Researchers followed participants for an average of about four years. Their main question was how long each treatment could keep a person’s average blood sugar, measured by an A1C test, below the study’s target.
Liraglutide and insulin glargine performed best at maintaining blood sugar control. People taking either of these treatments generally stayed below the target longer than people taking sitagliptin or glimepiride.
The difference was meaningful but not enormous. Compared with sitagliptin, which was the least effective of the four treatments for maintaining the target, liraglutide and insulin glargine kept blood sugar controlled for roughly six months longer on average.
The results were generally similar among people of different ages, sexes, races and ethnic groups. This suggested that the overall differences between the medicines were not limited to one particular demographic group.
Still, the study revealed how difficult long-term diabetes management can be. About three out of four participants eventually had blood sugar rise above the target despite taking metformin plus one of the additional treatments.
Researchers also examined other outcomes because blood sugar is only one part of diabetes care. Heart and blood vessel disease is a major concern for people with type 2 diabetes, so cardiovascular events were closely monitored.
Liraglutide showed an additional advantage in this area. Participants assigned to liraglutide had fewer cardiovascular events overall than those assigned to the other three treatments, although treatment decisions must also consider side effects, cost, weight changes and how each medicine is taken.
Each treatment had its own advantages and disadvantages. For example, insulin and glimepiride can increase the risk of blood sugar falling too low, while liraglutide is injected and can cause digestive side effects in some people.
The major GRADE findings were published in The New England Journal of Medicine. The study was supported by the U.S. National Institute of Diabetes and Digestive and Kidney Diseases and involved researchers and medical centers across the country.
The findings do not identify one medicine that is best for every person with type 2 diabetes. Instead, they give doctors stronger evidence for comparing treatment options after metformin is no longer enough on its own.
Choosing a diabetes medicine depends on more than its ability to lower blood sugar. A person’s heart and kidney health, risk of low blood sugar, body weight, other medical conditions, treatment preferences and access to medication can all influence the best choice.
The GRADE study also shows why diabetes treatment often needs to change over time. Regular monitoring and adjustments can help people maintain better blood sugar control and reduce their risk of serious complications as the condition progresses.
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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