Type 2 Diabetes Mellitus (T2DM)
Conditions
Keywords
type 2 diabetes, basal insulin, vildagliptin
Brief summary
To compare a therapeutic strategy combining vildagliptin+metformin + Basal Insulin versus SU+metformin + Basal Insulin on the incidence of hypoglycemic events over 24 weeks.
Detailed description
This study, conducted in T2DM patients failing a dual therapy with metformin/SU in whom the decision to start basal insulin has been taken, will compare vildagliptin+metformin versus the previously used SU+met combination (regimen kept unchanged) in association with basal insulin, up-titrated as per usual algorithms primarily based on FPG to obtain a similar improvement in glycemic control in both arms, on the incidence of hypoglycemic episodes over 24 weeks.
Interventions
DRUGVildagliptin
50 mg b.i.d
DRUGMetformin
metformin is to be kept unchanged
DRUGsulfonylurea (SU)
DRUGBasal Insulin
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* T2DM patients inadequately controlled with metformin+ SU combination therapy at max tolerated doses and in whom the decision to start basal insulin has been taken * with stable metformin+ SU combination therapy for at least 12 weeks prior to randomization * with a glycemic target of HbA1c \<= 7% * with HbA1c at inclusion \>7% and \<=9% * Patients willing and able to start basal insulin and perform appropriate self monitoring of blood glucose (SMBG)
Exclusion criteria
* contraindication for either SUs, metformin or insulin and history of hypersensitivity to vildagliptin * acute or chronic diseases that interfere with efficacy/safety results of this trial or put patient at risk Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Patients Who Reported at Least One Symptomatic Hypoglycemic Event During the 24 Week Randomized Period in Both Treatment Arms | 24 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c to Week 24 in Both Treatment Arms | Baseline, Week 24 | — |
| Change From Baseline in Body Weight in Both Treatment Arms | Baseline, Week 24 | — |
| Percentage of Patients Reaching Their Glycemic Target Without Hypoglycemic Events | 24 weeks | Glycemic target is defined as Glycated hemoglobin(HbA1c) ≤ 7% |
| Percentage of Patients With Severe and Confirmed Hypoglycemic Events | 24 weeks | Severe hypoglycemic events (and number of events) , defined as events requiring assistance of a third party, and with confirmed hypoglycemic events (and number of events) defined as events with concomitant self monitoring of blood glucose (SMBG) \< 70 mg/dL |
| Percent of Participants That Reach Therapeutic Goal (HbA1c ≤ 7%) at Week 24 Without Any Hypoglycaemic Episode (Symptomatic or Not) and Without Any Weight Gain (Variation ≥3% Compared to Baseline) | week 24 | HbA1c \<= 7% without any hypoglycaemic episode (symptomatic or not) and without any weight gain |
| Mean Daily Insulin Dose at Week 24 | Week 24 | — |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Metformin/Vildagliptin + Basal Insulin Randomized patient will receive Vildagliptin 50 mg twice daily (b.i.d) + continued therapy with Metformin, + start of Basal Insulin up-titrated as per usual algorithms primarily based on FPG | 21 |
| SU+Metformin + Basal Insulin Randomized patient will remain on their previous dual therapy by SU+metformin, which will be kept unchanged, + start of Basal Insulin up-titrated as per usual algorithms primarily based on FPG | 21 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | antidiabetic drug prematurely stopped | 1 | 1 |
| Overall Study | Other reason | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Metformin/Vildagliptin + Basal Insulin | SU+Metformin + Basal Insulin | Total |
|---|---|---|---|
| Age, Continuous | 60.6 years STANDARD_DEVIATION 12.52 | 66.8 years STANDARD_DEVIATION 7.8 | 63.7 years STANDARD_DEVIATION 10.77 |
| Sex: Female, Male Female | 10 Participants | 8 Participants | 18 Participants |
| Sex: Female, Male Male | 11 Participants | 13 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 21 | 10 / 21 |
| serious Total, serious adverse events | 0 / 21 | 0 / 21 |
Outcome results
Primary
Percentage of Patients Who Reported at Least One Symptomatic Hypoglycemic Event During the 24 Week Randomized Period in Both Treatment Arms
Time frame: 24 weeks
Population: safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Metformin/Vildagliptin + Basal Insulin | Percentage of Patients Who Reported at Least One Symptomatic Hypoglycemic Event During the 24 Week Randomized Period in Both Treatment Arms | 22.2 percent of participants |
| SU+Metformin + Basal Insulin | Percentage of Patients Who Reported at Least One Symptomatic Hypoglycemic Event During the 24 Week Randomized Period in Both Treatment Arms | 45.0 percent of participants |
p-value: 0.139Chi-squared
Secondary
Change From Baseline in Body Weight in Both Treatment Arms
Time frame: Baseline, Week 24
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin/Vildagliptin + Basal Insulin | Change From Baseline in Body Weight in Both Treatment Arms | -0.3 kg | Standard Deviation 2.51 |
| SU+Metformin + Basal Insulin | Change From Baseline in Body Weight in Both Treatment Arms | 1.4 kg | Standard Deviation 2.61 |
Secondary
Change From Baseline in HbA1c to Week 24 in Both Treatment Arms
Time frame: Baseline, Week 24
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Metformin/Vildagliptin + Basal Insulin | Change From Baseline in HbA1c to Week 24 in Both Treatment Arms | week 24 | 7.2 HbA1c percent | Standard Deviation 0.71 |
| Metformin/Vildagliptin + Basal Insulin | Change From Baseline in HbA1c to Week 24 in Both Treatment Arms | baseline | 8.2 HbA1c percent | Standard Deviation 0.56 |
| SU+Metformin + Basal Insulin | Change From Baseline in HbA1c to Week 24 in Both Treatment Arms | baseline | 8.2 HbA1c percent | Standard Deviation 0.42 |
| SU+Metformin + Basal Insulin | Change From Baseline in HbA1c to Week 24 in Both Treatment Arms | week 24 | 7.4 HbA1c percent | Standard Deviation 0.89 |
Secondary
Mean Daily Insulin Dose at Week 24
Time frame: Week 24
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin/Vildagliptin + Basal Insulin | Mean Daily Insulin Dose at Week 24 | 33.0 (U/d) | Standard Deviation 23.08 |
| SU+Metformin + Basal Insulin | Mean Daily Insulin Dose at Week 24 | 19.8 (U/d) | Standard Deviation 13.83 |
Secondary
Percentage of Patients Reaching Their Glycemic Target Without Hypoglycemic Events
Glycemic target is defined as Glycated hemoglobin(HbA1c) ≤ 7%
Time frame: 24 weeks
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Metformin/Vildagliptin + Basal Insulin | Percentage of Patients Reaching Their Glycemic Target Without Hypoglycemic Events | 44.4 percent of participants |
| SU+Metformin + Basal Insulin | Percentage of Patients Reaching Their Glycemic Target Without Hypoglycemic Events | 47.4 percent of participants |
Secondary
Percentage of Patients With Severe and Confirmed Hypoglycemic Events
Severe hypoglycemic events (and number of events) , defined as events requiring assistance of a third party, and with confirmed hypoglycemic events (and number of events) defined as events with concomitant self monitoring of blood glucose (SMBG) \< 70 mg/dL
Time frame: 24 weeks
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Metformin/Vildagliptin + Basal Insulin | Percentage of Patients With Severe and Confirmed Hypoglycemic Events | 0.0 percent participants |
| SU+Metformin + Basal Insulin | Percentage of Patients With Severe and Confirmed Hypoglycemic Events | 0.0 percent participants |
Secondary
Percent of Participants That Reach Therapeutic Goal (HbA1c ≤ 7%) at Week 24 Without Any Hypoglycaemic Episode (Symptomatic or Not) and Without Any Weight Gain (Variation ≥3% Compared to Baseline)
HbA1c \<= 7% without any hypoglycaemic episode (symptomatic or not) and without any weight gain
Time frame: week 24
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Metformin/Vildagliptin + Basal Insulin | Percent of Participants That Reach Therapeutic Goal (HbA1c ≤ 7%) at Week 24 Without Any Hypoglycaemic Episode (Symptomatic or Not) and Without Any Weight Gain (Variation ≥3% Compared to Baseline) | 27.8 percent of participants |
| SU+Metformin + Basal Insulin | Percent of Participants That Reach Therapeutic Goal (HbA1c ≤ 7%) at Week 24 Without Any Hypoglycaemic Episode (Symptomatic or Not) and Without Any Weight Gain (Variation ≥3% Compared to Baseline) | 21.1 percent of participants |