Adipotide dosage regimen. To obtain a safe, steady‐state adipotide concentration, we recommend that patients use only once‐daily capsules. The optimal starting dose of adipotide was approximately 90 mg/day. Because of the slow elimination of adipotide, once‐daily adipotide dosing produces steady‐state levels that are approximately four times greater than the minimal concentration required for efficacy.
What is Adipotide Dosage used for?
The steady‐state adipotide plasma concentration is determined primarily by the once‐daily capsule dosage. Therefore, patients should not exceed 240 mg/day, because the total 24‐h concentration would exceed the steady‐state 24‐h trough concentration of 100 ng/mL. Although the use of a higher adipotide dose did not appear to confer any further benefit in this study, this finding requires confirmation in further trials.
Adipotide personal experience
As adiponectin increases with adipotide treatment in a dose‐dependent manner, there appears to be little additional clinical benefit to a doubling of the adiponectin level. The adverse event rate in this study was comparable to that seen in our previous studies of adipotide in combination with insulin, which showed a rate of 16% of patients having an adverse event, of whom 6% withdrew because of a serious adverse event.14 Adiponectin has previously been shown to be safe and well tolerated.13 In a phase II study, an increase in haemoglobin A1c (HbA1c) was found in a patient who received a continuous infusion of adiponectin to reach a plasma concentration of 150 μg/mL; however, this patient also received a concomitant high‐dose (800 mg) of pioglitazone.15
The adverse event profile of adiponectin in humans has been reported previously.14, 15 The primary reported adverse events included increased levels of liver enzymes, particularly aminotransferase and γ‐glutamyl transferase, in approximately 40% of patients.14 Another group has reported a high incidence of transient hypoglycaemia, as well as gastrointestinal adverse events such as nausea and flatulence. In addition, a phase II study of adiponectin for the treatment of cancer‐related cachexia showed an increased incidence of thrombocytosis, and a number of studies have shown an association between adiponectin and reduced platelet activity.18
What is the Best Adipotide Dosage?
However, these findings are likely related to the concomitant use of anticoagulants and antiplatelet agents and not adiponectin itself. Adiponectin is also being investigated in the treatment of non‐alcoholic steatohepatitis, a syndrome in which hepatocyte fatty acid accumulation and insulin resistance lead to hepatic fibrosis and cirrhosis.
A large randomized clinical trial of adiponectin for the treatment of non‐alcoholic steatohepatitis is in progress (AdipoHepat, ClinicalTrials.gov: NCT00734474). In conclusion, our results show that once‐daily adipotide can increase adiponectin levels to a therapeutic level in patients with type 2 diabetes. However, the benefit of using adiponectin in this study could not be clearly distinguished from the benefits associated with the improvements in haemoglobin A1c and insulin sensitivity that occur with insulin glargine alone.
This study also confirms the safety profile of adiponectin reported in previous clinical studies in patients with type 2 diabetes. The findings from this study will contribute to our understanding of the mechanism of action of adiponectin in patients with diabetes, and they will contribute to future studies that examine the effects of adiponectin on glucose metabolism in people with diabetes. The authors thank Michael E. Smith, MD, DVM, who conducted the study and provided medical supervision.
He is an employee of Sanofi. Medical writing support was provided by Sarah Spellman, PhD, and Michelle O’Dell of Fishawack Communications, and funded by Sanofi. Author contributions All authors have reviewed and commented on this manuscript, and have seen and approved the final version. Conflict of interest P. J. D. has served on advisory boards, as a consultant or speaker for Abbott, AstraZeneca, BD, BMS, Boehringer Ingelheim, GlaxoSmithKline, Eli Lilly, Merck, Pfizer, Novartis, Novo Nordisk, Roche and Sanofi. P. B. has received honoraria from Abbott, BD, BMS, Eli Lilly, Johnson & Johnson, Novartis, Novo Nordisk, Roche and Sanofi. M. R. has received research grants from AstraZeneca, BD, BMS, Eli Lilly, Novo Nordisk, Roche, Sanofi and Takeda.
C. T. was employed by Sanofi at the time the study was conducted. M. W. has received research grants from Novartis, Novo Nordisk, Sanofi and AstraZeneca, and is a consultant for Novo Nordisk. S. B. has received research grants from Sanofi, and is a consultant for Sanofi. S. E. has received research grants from Sanofi, and is a consultant for Sanofi, Abbott, AstraZeneca, Boehringer Ingelheim, BMS, GSK, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi and Takeda.