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

Primary Purpose

Ketosis Prone Diabetes, Diabetes Ketoacidosis, Hyperglycemia

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

metformin

placebo

Sitagliptin

About this trial

This is an interventional treatment trial for Ketosis Prone Diabetes

Eligibility Criteria

19 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

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).
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:

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.

Sites / Locations

Grady Memorial Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Metformin

Sitagliptin

Placebo

Arm Description

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).

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).

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT01099618

First Posted

March 15, 2010

Last Updated

May 30, 2015

Sponsor

Dawn Smiley MD

1. Study Identification

Unique Protocol Identification Number

NCT01099618

Brief Title

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

Interventional

2. Study Status

Record Verification Date

May 2014

Overall Recruitment Status

Completed

Study Start Date

March 2010 (undefined)

Primary Completion Date

February 2014 (Actual)

Study Completion Date

August 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Dawn Smiley MD

4. Oversight

Data Monitoring Committee

Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Ketosis Prone Diabetes, Diabetes Ketoacidosis, Hyperglycemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

48 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Metformin

Arm Type

Active Comparator

Arm Description

Arm Title

Sitagliptin

Arm Type

Active Comparator

Arm Description

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).

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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).

Intervention Type

Drug

Intervention Name(s)

metformin

Other Intervention Name(s)

Glucophage

Intervention Description

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

Intervention Name(s)

placebo

Intervention Description

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

Intervention Name(s)

Sitagliptin

Other Intervention Name(s)

Januvia

Intervention Description

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.

Primary Outcome Measure Information:

Title

Length of Remission

Description

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.

Time Frame

3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

19 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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). 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: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dawn D. Smiley, MD

Organizational Affiliation

Emory School of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Grady Memorial Hospital

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30303

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

32475838

Citation

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.

Results Reference

derived

PubMed Identifier

27573938

Citation

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.

Results Reference

derived

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

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