Type 2 Diabetes
Conditions
Brief summary
To evaluate the effect of DPP-4 inhibition on glucagon counter-regulatory mechanisms at moderate hypoglycemia in metformin-treated subjects with T2DM
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.
Interventions
DRUGSitagliptin
Sitagliptin 100 mg daily
DRUGPlacebo
Placebo one tablet daily
Sponsors
Merck Sharp & Dohme LLC
Lund University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
65 Years to 90 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glucagon Counterregulation to Hypoglycemia | Four weeks treatment | Change in plasma glucagon to insulin-induced hypoglycemia after four weeks of treatment with sitagliptin and placebo |
Countries
Sweden
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin First, Then Placebo Hypoglycemia clamp with sitagliptin
Sitagliptin: Treatment with sitagliptin 100mg QD for four weeks followed by hyperinsulinemic hypoglycemic clamp | 15 |
| Placebo First, Then Stagliptin Hypoglycemia clamp with placebo
Placebo: Treatment with placebo QD for four weeks followed by hyperinsulinemic hypoglycemic clamp | 13 |
| Total | 28 |
Baseline characteristics
| Characteristic | Sitagliptin First, Then Placebo | Placebo First, Then Stagliptin | Total |
|---|---|---|---|
| Age, Customized | 75.0 years STANDARD_DEVIATION 5.9 | 71.9 years STANDARD_DEVIATION 5.7 | 73.6 years STANDARD_DEVIATION 5.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 13 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Fasting glucagon | 29.5 pmol/l STANDARD_DEVIATION 9.7 | 30.0 pmol/l STANDARD_DEVIATION 12.2 | 29.8 pmol/l STANDARD_DEVIATION 10.9 |
| Region of Enrollment Sweden | 15 participants | 13 participants | 28 participants |
| Sex: Female, Male Female | 7 Participants | 5 Participants | 12 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 13 | 0 / 28 | 0 / 28 |
| other Total, other adverse events | 0 / 15 | 0 / 13 | 0 / 28 | 0 / 28 |
| serious Total, serious adverse events | 0 / 15 | 0 / 13 | 0 / 28 | 0 / 28 |
Outcome results
Primary
Glucagon Counterregulation to Hypoglycemia
Change in plasma glucagon to insulin-induced hypoglycemia after four weeks of treatment with sitagliptin and placebo
Time frame: Four weeks treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Glucagon Counterregulation to Hypoglycemia | 16.0 pmol/l | Standard Error 2.9 |
| Placebo | Glucagon Counterregulation to Hypoglycemia | 16.5 pmol/l | Standard Error 2.8 |