New research shows that glipulin, a glucagon-like peptide-1 receptor added to insulin, helps reduce the variability of blood sugar levels in patients with Type 2 diabetes, according to a multi-institutional clinical trial that included researchers from The University of Texas School of Public Health. The school is part of The University of Texas Health Science Center at Houston (UTHealth).
Called FLATSUGAR (FLuctuATion reduction with inSUlin and Glp-1 Added togetheR), the study seeks to determine which diabetes therapies work best to reduce blood sugar fluctuations. Good blood sugar control is essential for preventing many of the disease’s life-threatening complications—including heart attack and stroke.
Researchers focused on reducing overall glycemic variability in study participants, rather than controlling HbA1c (glycated hemoglobin), the gold standard used to reflect blood glucose levels.
“The ups and downs of glucose, on top of elevated HbA1c levels may also be responsible for complications,” explains Dr. Barry R. Davis, director of the Coordinating Center for Clinical Trials and principal investigator for the data coordinating center at The University of Texas School of Public Health. Dr. Jeffrey Probstfield and Dr. Irl Hirsch of the University of Washington were the study’s principal investigators.
Study results were reported at the annual meeting of the American Diabetes Association and an overview of the study’s design was published in Diabetes Care in June.
Accounting for about 90 to 95 percent of all diagnosed cases of diabetes, Type 2 diabetes is caused when the body’s cells fail to respond to insulin. Doctors routinely treat the condition with oral drugs, most notably metformin, and may prescribe insulin therapy. But keeping blood sugar levels steady can be a challenge and too much insulin may lead to hypoglycemia and weight gain.
Over the course of the six-month study, researchers screened 255 patients with Type 2 diabetes with 102 randomized to one of two treatment groups and followed for 26 weeks. All patients received metformin and basal insulin treatment (a long-acting form of insulin) using once- or twice-daily insulin, plus a bolus rapid-acting insulin analog (insulin specifically taken at meal times). They were then randomized to either continue to use bolus insulin at mealtimes or to use the GLP-1 agonist exenatide instead of bolus insulin.
Participants underwent masked continuous glucose monitoring to assess their glucose control, and Holter monitoring to register changes in heart function. Researchers also measured HbA1c, weight, markers of inflammation and cardiovascular risk and albuminuria (more than the normal amount of albumin in the urine–a sign of significant kidney disease).