Trial Outcomes & Findings for Remission Evaluation of a Metabolic Intervention in Type 2 Diabetes With Forxiga (NCT NCT02561130)

NCT ID: NCT02561130

Last Updated: 2020-11-24

Results Overview

Drug-free diabetes remission is defined as HbA1C \< 6.5 % off glucose-lowering agents for at least 12 weeks.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 154 participants
• Primary outcome timeframe: 24 weeks after randomization
• Results posted on: 2020-11-24

Participant Flow

Participant milestones

Measure	Intervention Drug: insulin glargine - sc injection; Drug: metformin, oral administration; Drug: forxiga, oral administration; Behavioral: lifestyle therapy, diet and exercise insulin glargine: Dose is titrated to achieve fasting normoglycemia metformin: Dose is titrated to 1 g bid or maximal tolerated dose Forxiga: Dose is titrated to 10 mg po daily or maximal tolerated dose Lifestyle therapy: Lifestyle intervention includes individualized dietary and exercise advice and frequent visits for goal reinforcement, behavior modification and problem-solving	Standard Care Standard glycemic care as informed by the current clinical practice guidelines
Overall Study STARTED	77	77
Overall Study COMPLETED	76	76
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Remission Evaluation of a Metabolic Intervention in Type 2 Diabetes With Forxiga

Baseline characteristics by cohort

Measure	Intervention n=77 Participants Drug: insulin glargine - sc injection; Drug: metformin, oral administration; Drug: forxiga, oral administration; Behavioral: lifestyle therapy, diet and exercise insulin glargine: Dose is titrated to achieve fasting normoglycemia metformin: Dose is titrated to 1 g bid or maximal tolerated dose Forxiga: Dose is titrated to 10 mg po daily or maximal tolerated dose Lifestyle therapy: Lifestyle intervention includes individualized dietary and exercise advice and frequent visits for goal reinforcement, behavior modification and problem-solving	Standard Care n=77 Participants Standard glycemic care as informed by the current clinical practice guidelines	Total n=154 Participants Total of all reporting groups
Age, Continuous	56.8 years STANDARD_DEVIATION 10.0 • n=5 Participants	56.7 years STANDARD_DEVIATION 9.6 • n=7 Participants	56.8 years STANDARD_DEVIATION 9.7 • n=5 Participants
Sex: Female, Male Female	27 Participants n=5 Participants	27 Participants n=7 Participants	54 Participants n=5 Participants
Sex: Female, Male Male	50 Participants n=5 Participants	50 Participants n=7 Participants	100 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	64 Participants n=5 Participants	61 Participants n=7 Participants	125 Participants n=5 Participants
Race/Ethnicity, Customized Non-Caucasian	13 Participants n=5 Participants	16 Participants n=7 Participants	29 Participants n=5 Participants
Region of Enrollment Canada	77 participants n=5 Participants	77 participants n=7 Participants	154 participants n=5 Participants
Duration of diabetes	37.7 months STANDARD_DEVIATION 26.7 • n=5 Participants	35.8 months STANDARD_DEVIATION 27.8 • n=7 Participants	36.8 months STANDARD_DEVIATION 27.2 • n=5 Participants
Glycated hemoglobin (HbA1C)	6.7 percentage of glycated hemoglobin STANDARD_DEVIATION 0.6 • n=5 Participants	6.7 percentage of glycated hemoglobin STANDARD_DEVIATION 0.7 • n=7 Participants	6.7 percentage of glycated hemoglobin STANDARD_DEVIATION 0.6 • n=5 Participants
Body Mass Index (BMI)	33.3 kg/m^2 STANDARD_DEVIATION 5.8 • n=5 Participants	32.5 kg/m^2 STANDARD_DEVIATION 6.0 • n=7 Participants	32.9 kg/m^2 STANDARD_DEVIATION 5.9 • n=5 Participants

PRIMARY outcome

Timeframe: 24 weeks after randomization

Drug-free diabetes remission is defined as HbA1C < 6.5 % off glucose-lowering agents for at least 12 weeks.

Outcome measures

Measure	Intervention n=77 Participants Drug: insulin glargine - sc injection; Drug: metformin, oral administration; Drug: forxiga, oral administration; Behavioral: lifestyle therapy, diet and exercise insulin glargine: Dose is titrated to achieve fasting normoglycemia metformin: Dose is titrated to 1 g bid or maximal tolerated dose Forxiga: Dose is titrated to 10 mg po daily or maximal tolerated dose Lifestyle therapy: Lifestyle intervention includes individualized dietary and exercise advice and frequent visits for goal reinforcement, behavior modification and problem-solving	Standard Care n=77 Participants Standard glycemic care as informed by the current clinical practice guidelines
Number of Participants Achieving Drug-free Diabetes Remission in the Experimental Group Compared to the Control Group	19 Participants	13 Participants

SECONDARY outcome

Timeframe: 64 weeks after randomization

Drug-free diabetes remission is defined as HbA1C < 6.5 % off glucose-lowering agents for at least 12 weeks.

Outcome measures

Measure	Intervention n=77 Participants Drug: insulin glargine - sc injection; Drug: metformin, oral administration; Drug: forxiga, oral administration; Behavioral: lifestyle therapy, diet and exercise insulin glargine: Dose is titrated to achieve fasting normoglycemia metformin: Dose is titrated to 1 g bid or maximal tolerated dose Forxiga: Dose is titrated to 10 mg po daily or maximal tolerated dose Lifestyle therapy: Lifestyle intervention includes individualized dietary and exercise advice and frequent visits for goal reinforcement, behavior modification and problem-solving	Standard Care n=77 Participants Standard glycemic care as informed by the current clinical practice guidelines
Number of Participants Achieving Drug-free Diabetes Remission	11 Participants	6 Participants

SECONDARY outcome

Timeframe: 24 weeks after randomization

Drug-free complete diabetes remission is defined as HbA1C < 6.0 % off glucose-lowering agents for at least 12 weeks.

Outcome measures

Measure	Intervention n=77 Participants Drug: insulin glargine - sc injection; Drug: metformin, oral administration; Drug: forxiga, oral administration; Behavioral: lifestyle therapy, diet and exercise insulin glargine: Dose is titrated to achieve fasting normoglycemia metformin: Dose is titrated to 1 g bid or maximal tolerated dose Forxiga: Dose is titrated to 10 mg po daily or maximal tolerated dose Lifestyle therapy: Lifestyle intervention includes individualized dietary and exercise advice and frequent visits for goal reinforcement, behavior modification and problem-solving	Standard Care n=77 Participants Standard glycemic care as informed by the current clinical practice guidelines
Number of Participants Achieving Drug-free HbA1C < 6.0%	6 Participants	6 Participants

SECONDARY outcome

Timeframe: 24 weeks

Diabetes relapse without overt hyperglycemia is defined as HbA1C 6.5-6.9% off glucose-lowering agents for at least 12 weeks.

Outcome measures

Measure	Intervention n=77 Participants Drug: insulin glargine - sc injection; Drug: metformin, oral administration; Drug: forxiga, oral administration; Behavioral: lifestyle therapy, diet and exercise insulin glargine: Dose is titrated to achieve fasting normoglycemia metformin: Dose is titrated to 1 g bid or maximal tolerated dose Forxiga: Dose is titrated to 10 mg po daily or maximal tolerated dose Lifestyle therapy: Lifestyle intervention includes individualized dietary and exercise advice and frequent visits for goal reinforcement, behavior modification and problem-solving	Standard Care n=77 Participants Standard glycemic care as informed by the current clinical practice guidelines
Number of Participants Achieving Diabetes Relapse Without Overt Hyperglycemia Off Diabetes Drugs	20 Participants	9 Participants

SECONDARY outcome

Timeframe: 12 weeks after randomization

Expressed in Diabetes Control and Complications Trial (DCCT) units

Outcome measures

Measure	Intervention n=77 Participants Drug: insulin glargine - sc injection; Drug: metformin, oral administration; Drug: forxiga, oral administration; Behavioral: lifestyle therapy, diet and exercise insulin glargine: Dose is titrated to achieve fasting normoglycemia metformin: Dose is titrated to 1 g bid or maximal tolerated dose Forxiga: Dose is titrated to 10 mg po daily or maximal tolerated dose Lifestyle therapy: Lifestyle intervention includes individualized dietary and exercise advice and frequent visits for goal reinforcement, behavior modification and problem-solving	Standard Care n=66 Participants Standard glycemic care as informed by the current clinical practice guidelines
Glycated Hemoglobin (HbA1C)	5.9 percentage of glycated hemoglobin Standard Deviation 0.4	6.6 percentage of glycated hemoglobin Standard Deviation 0.7

SECONDARY outcome

Timeframe: During 64 weeks of follow-up

Symptomatic hypoglycemic episode is defined as an event with clinical symptoms consistent with hypoglycemia.

Outcome measures

Measure	Intervention n=77 Participants Drug: insulin glargine - sc injection; Drug: metformin, oral administration; Drug: forxiga, oral administration; Behavioral: lifestyle therapy, diet and exercise insulin glargine: Dose is titrated to achieve fasting normoglycemia metformin: Dose is titrated to 1 g bid or maximal tolerated dose Forxiga: Dose is titrated to 10 mg po daily or maximal tolerated dose Lifestyle therapy: Lifestyle intervention includes individualized dietary and exercise advice and frequent visits for goal reinforcement, behavior modification and problem-solving	Standard Care n=77 Participants Standard glycemic care as informed by the current clinical practice guidelines
Number of Participants With Non-severe Symptomatic Hypoglycemic Episodes	34 Participants	15 Participants

SECONDARY outcome

Timeframe: 12 weeks after randomization

(Weight at randomization - weight at 12 weeks)/(weight at randomization)

Outcome measures

Measure	Intervention n=76 Participants Drug: insulin glargine - sc injection; Drug: metformin, oral administration; Drug: forxiga, oral administration; Behavioral: lifestyle therapy, diet and exercise insulin glargine: Dose is titrated to achieve fasting normoglycemia metformin: Dose is titrated to 1 g bid or maximal tolerated dose Forxiga: Dose is titrated to 10 mg po daily or maximal tolerated dose Lifestyle therapy: Lifestyle intervention includes individualized dietary and exercise advice and frequent visits for goal reinforcement, behavior modification and problem-solving	Standard Care n=64 Participants Standard glycemic care as informed by the current clinical practice guidelines
Percentage of Weight Loss From Baseline	2.9 percentage of weight loss Standard Deviation 3.2	1.0 percentage of weight loss Standard Deviation 2.5

SECONDARY outcome

Timeframe: 12 weeks after randomization

(Waist circumference at 12 weeks - waist circumference at randomization)

Outcome measures

Measure	Intervention n=76 Participants Drug: insulin glargine - sc injection; Drug: metformin, oral administration; Drug: forxiga, oral administration; Behavioral: lifestyle therapy, diet and exercise insulin glargine: Dose is titrated to achieve fasting normoglycemia metformin: Dose is titrated to 1 g bid or maximal tolerated dose Forxiga: Dose is titrated to 10 mg po daily or maximal tolerated dose Lifestyle therapy: Lifestyle intervention includes individualized dietary and exercise advice and frequent visits for goal reinforcement, behavior modification and problem-solving	Standard Care n=64 Participants Standard glycemic care as informed by the current clinical practice guidelines
Change in Waist Circumference From Baseline	-3.0 cm Standard Deviation 4.1	-1.3 cm Standard Deviation 3.3

SECONDARY outcome

Timeframe: During 64 weeks of follow-up

Severe hypoglycemic episode is defined as an event with clinical symptoms consistent with hypoglycemia in which the participant required the assistance of another person, and one of the following: (i) the event was associated with a documented self-measured or laboratory plasma glucose level </= 2.0 mmol/L or (ii) the event was associated with prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration.

Outcome measures

Measure	Intervention n=77 Participants Drug: insulin glargine - sc injection; Drug: metformin, oral administration; Drug: forxiga, oral administration; Behavioral: lifestyle therapy, diet and exercise insulin glargine: Dose is titrated to achieve fasting normoglycemia metformin: Dose is titrated to 1 g bid or maximal tolerated dose Forxiga: Dose is titrated to 10 mg po daily or maximal tolerated dose Lifestyle therapy: Lifestyle intervention includes individualized dietary and exercise advice and frequent visits for goal reinforcement, behavior modification and problem-solving	Standard Care n=77 Participants Standard glycemic care as informed by the current clinical practice guidelines
Number of Participants With Severe Hypoglycemic Episodes	0 Participants	0 Participants

Adverse Events

Intervention

Serious events: 3 serious events

Other events: 12 other events

Deaths: 0 deaths

Standard Care

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Measure	Intervention n=77 participants at risk Drug: insulin glargine - sc injection; Drug: metformin, oral administration; Drug: forxiga, oral administration; Behavioral: lifestyle therapy, diet and exercise insulin glargine: Dose is titrated to achieve fasting normoglycemia metformin: Dose is titrated to 1 g bid or maximal tolerated dose Forxiga: Dose is titrated to 10 mg po daily or maximal tolerated dose Lifestyle therapy: Lifestyle intervention includes individualized dietary and exercise advice and frequent visits for goal reinforcement, behavior modification and problem-solving	Standard Care n=77 participants at risk Standard glycemic care as informed by the current clinical practice guidelines
Hepatobiliary disorders Cholecystitis	1.3% 1/77 • Number of events 1 • 64 weeks	0.00% 0/77 • 64 weeks
Gastrointestinal disorders Viral gastroenteritis	1.3% 1/77 • Number of events 1 • 64 weeks	0.00% 0/77 • 64 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Resection of liver metastases from colorectal cancer	1.3% 1/77 • Number of events 1 • 64 weeks	0.00% 0/77 • 64 weeks

Other adverse events

Measure	Intervention n=77 participants at risk Drug: insulin glargine - sc injection; Drug: metformin, oral administration; Drug: forxiga, oral administration; Behavioral: lifestyle therapy, diet and exercise insulin glargine: Dose is titrated to achieve fasting normoglycemia metformin: Dose is titrated to 1 g bid or maximal tolerated dose Forxiga: Dose is titrated to 10 mg po daily or maximal tolerated dose Lifestyle therapy: Lifestyle intervention includes individualized dietary and exercise advice and frequent visits for goal reinforcement, behavior modification and problem-solving	Standard Care n=77 participants at risk Standard glycemic care as informed by the current clinical practice guidelines
Infections and infestations Genitourinary infection	5.2% 4/77 • Number of events 5 • 64 weeks	1.3% 1/77 • Number of events 1 • 64 weeks
Infections and infestations Other infections	0.00% 0/77 • 64 weeks	3.9% 3/77 • Number of events 3 • 64 weeks
Infections and infestations Abscess drainage	2.6% 2/77 • Number of events 2 • 64 weeks	0.00% 0/77 • 64 weeks
Injury, poisoning and procedural complications Injury	3.9% 3/77 • Number of events 4 • 64 weeks	0.00% 0/77 • 64 weeks
General disorders Abdominal pain	3.9% 3/77 • Number of events 3 • 64 weeks	0.00% 0/77 • 64 weeks
Renal and urinary disorders Moderate renal dysfunction defined as GFR 30-60 ml/min/1.73m2	1.3% 1/77 • Number of events 1 • 64 weeks	7.8% 6/77 • Number of events 6 • 64 weeks

Additional Information

Natalia McInnes

McMaster University

Phone: 905-521-2100

Email: natalia.mcinnes@mcmaster.ca

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place