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

NCT01099618 | Completed Phase 4 Results DMC

• 1 other identifier: IRB00026272
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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.

Conditions

Ketosis Prone Diabetes; Diabetes Ketoacidosis; Hyperglycemia

Outcome Measures

Primary Outcomes (1)

• Length of Remission

  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.

  3 years

Study Arms (3)

Metformin

ACTIVE COMPARATOR

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

Sitagliptin

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

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

Interventions

metformin DRUG

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.

Also known as: Glucophage

Metformin

placebo DRUG

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.

Placebo

Sitagliptin DRUG

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.

Also known as: Januvia

Sitagliptin

Eligibility Criteria

• Age: 19 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The hyperglycemic group will include patients with an admission plasma glucose \> 400 mg/dL but without the presence of metabolic acidosis or ketosis.

You may not qualify if:

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

Sponsors & Collaborators

• Dawn Smiley MD: lead

Study Sites (1)

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

Related Publications (2)

• 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):e001062. doi: 10.1136/bmjdrc-2019-001062.

  PMID: 32475838 DERIVED

• 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. doi: 10.2337/dc16-0406. Epub 2016 Aug 29.

  PMID: 27573938 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Hyperglycemia

Interventions

Metformin; Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Results Point of Contact

• Title: Dawn Smiley
• Organization: Emory University SOM

dsmiley@emory.edu

4047781665

Study Officials

• Dawn D. Smiley, MD

  Emory School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 15, 2010
• First Posted: April 7, 2010
• Study Start: March 1, 2010
• Primary Completion: February 1, 2014
• Study Completion: August 1, 2014
• Last Updated: June 18, 2015
• Results First Posted: June 18, 2015

Record last verified: 2014-05

Locations

US (1)