DiabetesDrugs & MedicationsPreventive Medicine


Everyone knows that patients with Diabetes Mellitus have trouble with their blood sugar—it’s too high! Blood sugar is the measurable marker that tells a patient, and the doctor, if diabetes is being controlled adequately. For better control, some patients check their blood sugar several times a day and make medication dosage adjustments based on the results. Theoretically, the lower the blood sugar, the better controlled is the diabetes. 

Of course, diabetes is more than just high blood sugar, and experts have long disagreed on many of the details. Does high blood sugar have a role in the multi-system expressions of diabetes? Does tight blood sugar control have a role in preventing the devastating problems associated with diabetes? Disagreements abound, but most physicians believe lowering the blood sugar is beneficial. 

To lower the blood sugar, diabetic patients take a variety of oral and/or injectable drugs. There are several classes of drugs for diabetes, and most patients take more than one. These drugs differ in the mechanism by which they lower the blood sugar, and some are clearly more effective than others. The results of a study comparing four commonly used blood sugar lowering drugs is the theme of this blogpost. 

The patients in this study were all Type II diabetics. That means their blood sugar was high because they have insulin antibodies that keep insulin from moving sugar out of the blood stream and into the cells. The patients were all on metformin, the first drug prescribed for most diabetics. It blocks absorption of sugar in the intestine, reduces sugar produced by the liver, and improves insulin sensitivity (makes it work better).

The four drugs in the study were:

     Glimepiride (Amaryl) — a sulfonylurea

     Liraglutide (Victoza) — a GLP-1 receptor analog

     Sitagliptin (Januvia) — a DPP-4 inhibitor

     Glargine Insulin (Lantus) — synthetic version of human insulin

There were 5047 patients with Type II diabetes followed for five years who were randomly assigned to take glargine, sitagliptin, liraglutide, or glimeperide. Patient control was monitored by frequent blood sugar measurements and hemoglobin A1C tests, and was achieved by lowering the A1C by 0.3 percentage points from baseline. The results of the study follow:

“Glargine and liraglutide were significantly….more effective than glimeperide and sitagliptin for achieving and maintaining targeted hemoglobin A1C levels. Sitagliptin was the least effective treatment.”

Glimeperide, a potent sulfonylurea, caused severe low blood sugar more often than any of the other three drugs. Hypoglycemia has always been a concern with sulfonylureas. 

Patients on “liraglutide experienced greater weight loss but also had more frequent gastrointestinal adverse effects.” GLP-1 drug manufacturers have touted weight loss as one reason to use this drug class. 

The bottom line of this study is “that older generic or bio-similar low-cost agents still have a role in the treatment of persons with early Type II diabetes who are at low cardiovascular risk.” The incidence of “microvascular complications and death were not substantially different among the treatment groups, but there appeared to be small differences in rates of any cardiovascular disease.”

Dr. G’s Opinion: This study proves all of these four drugs will lower blood sugar; the injectables, glargine insulin and liraglutide, most effectively. But lowering blood sugar is only part of the treatment. Microvascular and cardiovascular complications of Type II diabetes are bigger problems and make diabetes the devastating disease it is. Drugs that reduce the complications of diabetes are preferable to those that merely lower blood sugar. Physicians need to learn which drugs have the greatest impact on the complications and use them preferentially. Pharmaceutical sales reps will be glad to tell you which ones they are.

Reference:  Clinical Trials Update : “Trial Compares Glucose-lowering Drugs for Type II Diabetes.” JAMA 2022 October 25;328(16):1581.

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