Feed-Back Suppression of Meal-Induced Glucagon-like Peptide 1 (GLP-1) Secretion

Launched by MICHAEL A. NAUCK · Apr 20, 2016

Keywords

ClinConnect Summary

Design. The present study is a phase I, single-centre, double-blind, randomized, cross-over (3 treatments, 3 treatment periods and 6 sequences), stratified (background medication: metformin vs. diet-only), placebo-controlled study, comparing periods lasting 6-9 days on treatment with repeated doses of vildagliptin, sitagliptin, or placebo, with wash-out periods between treatment periods lasting 21 days minimum.

Experimental procedures. Meal tests were performed in the morning after an overnight fast. The standardized mixed meal was composed of 2 eggs (100 g), 1 slice (50 g) of whole grain ...

Gender

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Eligibility criteria

• Inclusion Criteria:
• • diabetes mellitus type 2 for more than one year, as defined by the American Diabetes Association
• • body-mass-index between 20.0 and 40.0 kg/m² (inclusive),
• • glycohaemoglobin (HbA1c) ≤ 8.5%,
• • normal vital signs after 10 minutes resting in the supine position: systolic blood pressure 96 mmHg -159 mmHg; diastolic blood pressure 46 mmHg-99 mmHg; heart rate 46-99 bpm
• • laboratory parameters within the normal range, or abnormalities judged to be clinically irrelevant by the investigator (serum estimated glomerular filtration rate was enforced to be \> 60 ml/min; hepatic enzymes and bilirubin (unless the subject has documented Gilbert syndrome) had to be \> 3-fold the upper limit of normal)
• • women of childbearing potential (less than two years post-menopausal or not surgically sterile for more than 3 months), had to prove a negative serum β-human chorionic gonadotropin (HCG) pregnancy test at screening and a negative urine β-HCG pregnancy test at day 1 on each of the treatment periods, had to use a highly effective method of birth control (failure rate less than 1% per year)
• • normal or clinically irrelevant findings in medical history and physical examination
• Exclusion Criteria:
• • any glucose-lowering drug therapy other than metformin during 3 months before the first treatment period
• • any history or presence of clinically relevant cardiovascular, pulmonary, gastro-intestinal, hepatic, renal, metabolic (apart from diabetes mellitus type 2), haematological, neurological, psychiatric, systemic, ocular, gynaecologic, or infectious disease; any acute infectious disease or signs of acute illness
• • symptoms of a clinically significant illness in the 3 months before the study, which, according to the investigator's opinion, could interfere with the purposes of the study
• • congestive heart failure of New York Heart Association (NYHA) functional class III-IV
• • Regular use of any medication other than metformin in the last month before study start with the exception of thyroid hormones, lipid-lowering and antihypertensive drugs, and, if female, with the exception of hormonal contraception or menopausal hormone replacement therapy
• • blood loss (\>300 ml, any reason) within 3 months before inclusion, or a haemoglobin \< 11.0 g/dl
• • participation in a trial with any investigational drug during the past three months
• • presence or history of a drug allergy or clinically significant allergic disease according to the investigator's judgment including any known hypersensitivity to DPP-4 inhibitors
• • presence of drug or alcohol abuse (alcohol consumption \> 40 grams / day)
• • if female, pregnancy (defined as positive β-HCG blood test), breast-feeding