Ketosis-Prone Diabetes Mellitus (KPDM): Metformin Versus Sitagliptin Treatment

• ClinicalTrials.gov Identifier: NCT01099618
• Recruitment Status: Completed
• First Posted: April 7, 2010
• Results First Posted: June 18, 2015
• Last Update Posted: June 18, 2015
• Sponsor: Dawn Smiley MD
• Information provided by (Responsible Party): Dawn Smiley MD, Emory University

Study Description

Brief Summary:

The study intends on enrolling 48 subjects with diabetes. Diabetic subjects that no longer need insulin will be randomly placed (like the flip of a coin) on a diabetes pill called metformin, a diabetes pill called sitagliptin or a placebo pill (a pill without active medication). Subjects on pills will be followed for 3½ years and undergo blood tests at specified intervals to assess their ability to make insulin. These studies will allow a better understanding of the factors that lead to high blood sugar in patients with ketosis-prone diabetes mellitus (KPDM) and direct the best diabetes treatment for this patient population.

Hypothesis: Metformin therapy or sitagliptin therapy compared to placebo, will improve β-cell function, insulin sensitivity, and allow for a longer period of time prior to encountering an insulin-deficient relapse after discontinuation of insulin therapy.

Condition or disease	Intervention/treatment	Phase
Ketosis Prone Diabetes; Diabetes Ketoacidosis; Hyperglycemia	Drug: metformin; Drug: placebo; Drug: Sitagliptin	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Ketosis-Prone Diabetes in African Americans: Predictive Markers, Underlying Mechanisms, and Treatment Outcomes: The Effects of Metformin vs. Sitagliptin on Beta-Cell Preservation in Obese Subjects With Ketosis-Prone Type 2 Diabetes Mellitus
• Study Start Date: March 2010
• Actual Primary Completion Date: February 2014
• Actual Study Completion Date: August 2014

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Metformin; All newly diagnosed subjects with KPDM that are able to discontinue insulin after 12 weeks or less will be randomized in double-blind fashion to receive either metformin 1000mg, sitagliptin 100mg or placebo once daily. Subjects that do not achieve remission will continue to receive insulin therapy and will discontinue the protocol. A total of 48 obese subjects with DKA (N=24) and obese subjects with hyperglycemia without ketoacidosis (n=24) will be equally randomized to receive metformin (MET) 1000 mg (n=16), sitagliptin (SIT) 100mg (n=16) or placebo (n=16).	Drug: metformin; The study subject will receive metformin (MET) 1000 mg tablet once a day as long as the patient maintains near-normoglycemic remission (BG < 130mg/dL and A1c <7%) during the 3-year follow-up period.; Other Name: Glucophage
Active Comparator: Sitagliptin; All newly diagnosed subjects with KPDM that are able to discontinue insulin after 12 weeks or less will be randomized in double-blind fashion to receive either metformin 1000 mg, sitagliptin 100mg or placebo once daily. Subjects that do not achieve remission will continue to receive insulin therapy and will discontinue the protocol. A total of 48 obese subjects with DKA (N=24) and obese subjects with hyperglycemia without ketoacidosis (n=24) will be equally randomized to receive metformin (MET) 1000 mg (n=16), sitagliptin (SIT) 100mg (n=16) or placebo (n=16).	Drug: Sitagliptin; The study subject will receive a sitagliptin 100mg once a day as long as the patient maintains near-normoglycemic remission (BG < 130mg/dL and A1c <7%) during the 3-year follow-up period.; Other Name: Januvia
Placebo Comparator: Placebo; All newly diagnosed subjects with KPDM that are able to discontinue insulin after 12 weeks or less will be randomized in double-blind fashion to receive either metformin 1000 mg, sitagliptin 100mg or placebo once daily. Subjects that do not achieve remission will continue to receive insulin therapy and will discontinue the protocol. A total of 48 obese subjects with DKA (N=24) and obese subjects with hyperglycemia without ketoacidosis (n=24) will be equally randomized to receive metformin (MET) 1000 mg(n=16), sitagliptin (SIT) 100mg (n=16) or placebo (n=16).	Drug: placebo; The study subject will receive a placebo tablet once a day as long as the patient maintains near-normoglycemic remission (BG < 130mg/dL and A1c <7%) during the 3-year follow-up period.

Outcome Measures

Primary Outcome Measures :

1. Length of Remission [ Time Frame: 3 years ]
   For those patients that are able to discontinue insulin therapy at or <12 weeks, how long were they able to well controlled with an A1c <7% on the agent that they were randomized to.

Eligibility Criteria

• Ages Eligible for Study: 19 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. All newly diagnosed overweight/obese (BMI >/=28 kg/m2) African-American patients with new-onset DKA and/or severe hyperglycemia and without apparent precipitating cause will be considered for inclusion into the study. The diagnosis of DKA will be established by standard criteria (blood glucose > 250 mg/dL, pH < 7.3, HCO3 < 18 mmol/L, increased anion gap).
2. The hyperglycemic group will include patients with an admission plasma glucose > 400 mg/dL but without the presence of metabolic acidosis or ketosis.

Exclusion Criteria:

1. significant medical or surgical illness, including but not limited to myocardial ischemia, congestive heart failure, chronic renal insufficiency, liver failure, and infectious processes;
2. recognized or suspected endocrine disorders associated with increased insulin resistance, such as hypercortisolism, acromegaly, or hyperthyroidism;
3. bleeding disorders, thrombocytopenia, or abnormalities in coagulation studies;
4. pregnancy,
5. have an allergy to any component of metformin or sitagliptin.

Contacts and Locations

Locations

United States, Georgia

Grady Memorial Hospital

Atlanta, Georgia, United States, 30303

Sponsors and Collaborators

Dawn Smiley MD

Investigators

• Principal Investigator: Dawn D. Smiley, MD; Emory School of Medicine

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Vellanki P, Stefanovski D, Anzola II, Smiley DD, Peng L, Umpierrez GE. Long-term changes in carbohydrate tolerance, insulin secretion and action in African-American patients with obesity and history of hyperglycemic crises. BMJ Open Diabetes Res Care. 2020 May;8(1). pii: e001062. doi: 10.1136/bmjdrc-2019-001062.

Vellanki P, Smiley DD, Stefanovski D, Anzola I, Duan W, Hudson M, Peng L, Pasquel FJ, Umpierrez GE. Randomized Controlled Study of Metformin and Sitagliptin on Long-term Normoglycemia Remission in African American Patients With Hyperglycemic Crises. Diabetes Care. 2016 Nov;39(11):1948-1955. Epub 2016 Aug 29.

• Responsible Party: Dawn Smiley MD, Principal Investigator, Emory University
• ClinicalTrials.gov Identifier: NCT01099618
• Other Study ID Numbers: IRB00026272
• First Posted: April 7, 2010
• Results First Posted: June 18, 2015
• Last Update Posted: June 18, 2015
• Last Verified: May 2014

Additional relevant MeSH terms:

Diabetes Mellitus; Hyperglycemia; Ketosis; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Acidosis; Acid-Base Imbalance; Autoimmune Diseases; Immune System Diseases; Metformin; Sitagliptin Phosphate; Hypoglycemic Agents; Physiological Effects of Drugs; Incretins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Dipeptidyl-Peptidase IV Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action