Tesamorelin treatment in patients with type 2 diabetes did not affect the primary endpoint of relative insulin response, a new study showed.
After patients were treated with the synthetic analogue of human growth hormone-releasing hormone (GHRH), relative insulin response — the study’s primary endpoint — there was no significant between-group differences regarding the change from baseline (0.020.08 L/pmol placebo; 0.050.37 1-mg tesamorelin; 0.130.56 2-mg tesamorelin), according to David Clemmons, MD, of the University of North Carolina at Chapel Hill, and colleagues.
The researchers also reported modifications to relevant diabetes medications, and the frequency of changes did not significantly differ between groups, as the team reported online in PLOS ONE.
However, there was a significant drop in total cholesterol levels among those on 2 mg of tesamorelin compared with placebo (-0.30.6 mmol/L; P
There were previous reports of an association between recombinant human growth hormone replacement therapy and reversal of metabolic alterations, stemming from low or deficient serum growth hormone levels, Clemmons et al noted. In addition, these analogues have also been linked to hyperglycemia, insulin resistance, and fluid retention, as well as worsening of glucose tolerance in prior studies. Therefore, the researchers aimed to evaluate the safety of administration of tesamorelin — known to increase basal and pulsatile secretion of growth hormone — in those with type 2 diabetes; the team said they were particularly interested in further evaluating usage in patients on highly active antiretroviral therapy.
A total of 53 people with type 2 diabetes were recruited from five U.S. centers for the randomized placebo-controlled trial. A 2-week “lead-in” period occurred following recruitment to determine dietary patterns and blood measurements of participants. Patients were randomized in a 1:1:1 fashion into three treatment groups: 1 mg of tesamorelin (n=18), 2 mg of tesamorelin (n=19), and placebo (n=16).
Blood samples were collected at baseline and subsequently every 4 weeks during the 12-week trial to assess fasting blood glucose, HbA1c, and IGF-1 levels. At the same time, a benchmark of a 75 g oral glucose tolerance test was also completed after an overnight fast, in which participants were also instructed to avoid insulin and sulfonylurea hypoglycemic medications. Triglyceride, total cholesterol, and LDL- and HDL-cholesterol were assessed through blood samples collected at baseline, and at 8 and 12 weeks.
In terms of overall diabetes control, there were no significant differences between the study groups. Regarding mean change (SD) in HbA1c levels — another secondary endpoint of the study — there was no overall treatment effect from baseline to 12 weeks between the groups. However, Clemmons’ group did find a significant difference at 12 weeks between the 2 mg tesamorelin and placebo groups (P
IGF-1 significantly increased among both treatment groups during the study period when compared with those in the placebo group (mean change from baseline: 33 ng/mL for the 1 mg group; 66 ng/mL for the 2 mg group; P
In terms of another secondary endpoint of fasting glucose levels (meanSD), there were also no significant differences from baseline to 12 weeks among the groups (P=0.44).
Week 1 data were as follows:
And for Week 12, the results were:
However, a borderline effect of time regarding fasting glucose levels was noted, with higher levels reported at weeks 4 and 8 among the 2 mg treatment group (P=0.06).
No serious adverse events or death were reported during the study. However, mild adverse events among the treatment groups included nausea, diarrhea, generalized weakness, fatigue, headache, light-headedness, and upper respiratory tract infection.
The researchers noted that their findings are in line with previous data, particularly one study that showed an initial rise in fasting glucose levels among patients on HIV treatment with tesamorelin, which then returned to baseline values after 6 months of treatment.
The study was sponsored by Theratechnologies, which also provided support in the form of the salary for one of the co-authors. Clemmons was a paid consultant of the company at the time the study was performed.
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Tesamorelin in T2D Not Linked to Metabolic Changes – MedPage Today