Sitagliptin and Glucagon Counterregulation (SITACLAMP)

The Effect of Sitagliptin on Glucagon Counterregulation and Incretin Hormones During Mild Hypoglycemia in Elderly Patients With Metformin-treated Type 2 Diabetes

To evaluate the effect of DPP-4 inhibition on glucagon counter-regulatory mechanisms at moderate hypoglycemia in metformin-treated subjects with T2DM

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Placebo; Drug: Sitagliptin

Detailed Description

The glucagon response to mild (3.0 mmol/l) hypoglycemia with and without DPP-4 inhibition by sitagliptin will be evaluated in elderly subjects with metformin treated type 2 diabetes to explore whether DPP-4 inhibition affects glucagon counter-regulation.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 4

Contacts and Locations

Study Locations

• Sweden
  • Malmö, Sweden, 20502
    • Skåne University Hospital Malmö

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 90 years (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Written consent has been given.
2. Patients with metformin treated T2DM (metformin dose >0,5 g/day and stable during the preceding 3 months)
3. Age >65 years.
4. HbA1c 6.0-8.5% (43-67 mmol/mol; inclusive) at visit 1.
5. Ability to complete the study

Exclusion Criteria:

1. A history of any secondary forms of diabetes, e.g., Cushing's syndrome and acromegaly.
2. Type 2 diabetes, positive GAD antibodies
3. eGFR <60 ml/min
4. Acute infections which may affect blood glucose control within 4 weeks prior to visit 1
5. Any history of recent (<2 weeks) recurrent or severe hypoglycemic episodes.
6. Liver disease such as cirrhosis or chronic active hepatitis
7. History of coronary heart disease or heart failure class III or IV
8. Donation of one unit (500 ml) or more of blood, significant blood loss equaling to at least one unit of blood within the past 2 weeks or a blood transfusion within the past 8 weeks.
9. Treatment with growth hormone of chronic oral or parenteral corticosteroid treatment (> 7 consecutive days of treatment) within 8 weeks prior to visit 1.
10. Use of other investigational drugs at visit 1 or within 30 days of visit 1, unsuitable for the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Sitagliptin first, then placebo; Sitagliptin treatment for four weeks, then washout for four weeks, then placebo for four weeks	Drug: Sitagliptin; Sitagliptin 100 mg daily
Other: Placebo first, then sitagliptin; Placebo for four weeks, then washout for four weeks, then sitagliptin for four weeks	Drug: Placebo; Placebo one tablet daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucagon Counterregulation to Hypoglycemia	Change in plasma glucagon to insulin-induced hypoglycemia after four weeks of treatment with sitagliptin and placebo	Four weeks treatment

Collaborators and Investigators

• Sponsor: Lund University
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2015
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: September 29, 2014
• First Submitted That Met QC Criteria: September 30, 2014
• First Posted (Estimate): October 3, 2014

Study Record Updates

• Last Update Posted (Actual): February 20, 2019
• Last Update Submitted That Met QC Criteria: October 14, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Sitagliptin Phosphate
• Other Study ID Numbers: 300A