Phase 1
Completed N=1,033
Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans
Source: ClinicalTrials.gov NCT01762046 ↗Enrolled (actual)
1,033
Serious AEs
0.0%
Results posted
May 2024
Primary outcomePrimary: Glipizide Response as Measured by Area Over the Glucose Curve Between Time 0 and 240 Minutes According to Genotype — 4893.5; 5032.6; 6011 mg/dl x time(minutes)
Summary
The SUGAR-MGH investigators are studying the influence of inherited gene variants on the response to two commonly prescribed type 2 diabetes medications, metformin and glipizide. They hypothesize that variants in genes that are associated with type 2 diabetes or related traits may impact the effect of anti-diabetic medications. In addition, physiological responses to an insulin secretagogue or an insulin sensitizer may shed light on the mechanism of action of reported genetic associations.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Glipizide Response as Measured by Area Over the Glucose Curve Between Time 0 and 240 Minutes According to Genotype |
4893.5; 5032.6; 6011 | — |
| PRIMARY Glipizide Response as Measured by Area Under the Insulin Curve Between Time 0 and 240 Minutes According to Genotype |
1141; 1278; 1400 | — |
| PRIMARY Metformin Response - Change in Fasting Glucose From Visit 1 to Visit 2 |
-2.1; -2.2; -6.1 | — |
| PRIMARY Metformin Response - Change in HOMA-IR From Visit 1 to Visit 2 |
0.09; 0.04; -0.45 | — |
| SECONDARY Incretin Levels |
1176.2; 1286.4; 1749.3; 879; 1060.8; 1415.7 | — |
| SECONDARY Proinsulin (Fasting) at Visit 1 and Visit 2 by Genotype for rs7903146 |
20.5; 23.4; 25.1; 19.4; 19.1; 21.4 | — |
| SECONDARY Fasting Glucagon at Visit 1 and Visit 2 by Genotype for rs7903146 |
29.9; 28.4; 25.7; 28.4; 28; 28.5 | — |
Eligibility Criteria
Inclusion Criteria
- Male or non-pregnant female > 18 years of age
- Investigators will target preferentially people at risk of diabetes or requiring diabetes meds
- The first tier of risk will be illustrated by one of the following variables (e.g. established type 2 diabetes on diet therapy alone, elevated random glucose in electronic medical record, PCOS, metabolic syndrome, obesity, history of gestational diabetes, etc.)
- The second tier of risk will be illustrated by other features that correlate with diabetes risk, such as a history of hypertension or dyslipidemia
- Otherwise healthy subjects may also be candidates for the study.
- Able and willing to give consent relevant to genetic investigation
Exclusion Criteria
- Pregnant, nursing or at risk of becoming pregnant
- Currently taking any medications for the treatment of diabetes
- Currently on metformin for any other indication (e.g. PCOS)
- Onset of diabetes in a family member before age 25, with autosomal transmission of diabetes across three generations
- History of liver or kidney disease
- Known severe allergic reactions to sulfonamides
- History of porphyria
- Documented estimated glomerular filtration rate (GFR) < 60 ml/min/1.73 m2, based on the most recent serum creatinine measurement available in the electronic medical record, and calculated by the Modification of Diet in Renal Disease equation (49) available at http://www.nephron.com/cgi-bin/MDRD\_GFR.cgi
- Currently taking medications known to affect glycemic parameters, such as glucocorticoids, growth hormone or fluoroquinolones
- Planned radiologic or angiographic study requiring contrast within one week of completion of this study
- Established coronary artery disease (CAD), defined as:
- History of myocardial infarction.
- History of revascularization (coronary artery bypass grafting, percutaneous coronary intervention (e.g. stenting or balloon angioplasty).
- Evidence of ischemia on cardiac stress test.
- Enrolled in any other interventional study at time of screening through completion of study protocol
- History of bariatric surgery
- History of seizures
- History of stroke/CVA
Data sourced from ClinicalTrials.gov (NCT01762046). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.