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

NCT ID: NCT01099618

Last Updated: 2015-06-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-03-31
• Study Completion Date: 2014-08-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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).

Group Type: ACTIVE_COMPARATOR

metformin

Intervention Type: 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.

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).

Group Type: ACTIVE_COMPARATOR

Sitagliptin

Intervention Type: 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.

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).

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Glucophage; Januvia

Eligibility 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.

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Dawn Smiley MD

OTHER

Sponsor Role: lead

Responsible Party

Dawn Smiley MD

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Dawn D. Smiley, MD

Role: PRINCIPAL_INVESTIGATOR

Emory School of Medicine

Locations

Grady Memorial Hospital

Atlanta, Georgia, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 32475838 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27573938 (View on PubMed)

Other Identifiers

IRB00026272

Identifier Type: -

Identifier Source: org_study_id