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A TREATMENT FOR ADULTS WITH TYPE 2 DIABETES MELLITUS, IN ADDITION TO DIET AND EXERCISEDapagliflozin as Add-On Therapy to Metformin

SIGNIFICANT REDUCTION IN A1C LEVELS

Primary end point: Mean reduction in A1C levels with dapagliflozin + metformin at 24 weeks1,2
Clinical trial result with significant reduction in A1C levels for Dapagliflozin as Add-On Therapy to Metformin with primary end point: Mean reduction in A1C levels with dapagliflozin + metformin at 24 weeks. Chart shows downward arrows for Dapagliflozin 5 mg + metformin (-0.7%) vs Dapagliflozin 10 mg + metformin (-0.8%) vs Placebo + metformin (-0.3%) against mean change from baseline A1C (%)Clinical trial result with significant reduction in A1C levels for Dapagliflozin as Add-On Therapy to Metformin with primary end point: Mean reduction in A1C levels with dapagliflozin + metformin at 24 weeks. Chart shows downward arrows for Dapagliflozin 5 mg + metformin (-0.7%) vs Dapagliflozin 10 mg + metformin (-0.8%) vs Placebo + metformin (-0.3%) against mean change from baseline A1C (%)

 

Values are last observation (prior to rescue for rescued patients) carried forward and represent adjusted mean change from baseline.

Dapagliflozin + metformin immediate-release were administered as separate tablets.

 

aP<0.0001 vs placebo + metformin.

BL=baseline.

SIGNIFICANT WEIGHT REDUCTION

Secondary end point: Mean weight reduction with dapagliflozin + metformin at 24 weeks1,2

Clinical trial result with significant weight reduction for Dapagliflozin as Add-On Therapy to Metformin where the secondary end point: mean weight reduction with dapagliflozin + metformin at 24 weeks. Chart shows downward arrows for Dapagliflozin 5 mg + metformin (-6.6lbs) vs Dapagliflozin 10mg + metformin (-6.4lbs) vs Placebo + metformin (-2.0lbs) against mean change from baseline weight (lbs)Clinical trial result with significant weight reduction for Dapagliflozin as Add-On Therapy to Metformin where the secondary end point: mean weight reduction with dapagliflozin + metformin at 24 weeks. Chart shows downward arrows for Dapagliflozin 5 mg + metformin (-6.6lbs) vs Dapagliflozin 10mg + metformin (-6.4lbs) vs Placebo + metformin (-2.0lbs) against mean change from baseline weight (lbs)

 

Values are last observation (prior to rescue for rescued patients) carried forward and represent adjusted mean change from baseline.

Dapagliflozin + metformin immediate-release were administered as separate tablets.

bP<0.0001 vs placebo + metformin.

BL=baseline.

XIGDUO XR is not indicated for weight loss.

SIGNIFICANTLY GREATER BLOOD PRESSURE REDUCTION

Other end point: Significant mean reduction in seated systolic blood pressure at 24 weeks1,2,c
Dapagliflozin as Add-On Therapy to Metformin clinical trials show significantly greater blood pressure reduction. Chart shows down arrows for Dapagliflozin 5 mg + Metformin XR vs Dapagliflozin 10 mg + metformin with Other end point: Significant mean reduction relative to metformin + placebo in seated systolic blood pressure at 24 weeks. Dapagliflozin 5 mg + metformin XR showed a mean change in seated systolic blood pressure (mm Hg) -4.5mm Hg and metformin XR + metformin -5.3 mm Hg.Dapagliflozin as Add-On Therapy to Metformin clinical trials show significantly greater blood pressure reduction. Chart shows down arrows for Dapagliflozin 5 mg + Metformin XR vs Dapagliflozin 10 mg + metformin with Other end point: Significant mean reduction relative to metformin + placebo in seated systolic blood pressure at 24 weeks. Dapagliflozin 5 mg + metformin XR showed a mean change in seated systolic blood pressure (mm Hg) -4.5mm Hg and metformin XR + metformin -5.3 mm Hg.

 

Values are last observation (including data after rescue) carried forward.

Dapagliflozin + metformin immediate-release were administered as separate tablets.


The metformin dose was =1500 mg per day.

cDapagliflozin was added on to patients uncontrolled on metformin monotherapy.

dP<0.05 vs metformin monotherapy.

BL=mean baseline.

Hypotension: Dapagliflozin causes intravascular volume contraction, and symptomatic hypotension can occur. Assess and correct volume status before initiating XIGDUO XR in patients with impaired renal function, elderly patients, or patients on loop diuretics. Monitor for hypotension.

XIGDUO XR is not indicated for the treatment of hypertension.

RATES OF HYPOGLYCEMIA

  • The frequency of hypoglycemia episodes was <5% and similar across treatment groups1,2
  • No major* episodes of hypoglycemia were reported1
  • No episode of hypoglycemia led to discontinuation from study2

*Major episodes of hypoglycemia were defined as symptomatic episodes requiring external (third-party) assistance due to severe impairment in consciousness or behavior with a capillary or plasma glucose value <54 mg/dL and prompt recovery after glucose or glucagon administration.

STUDY1
# of Patients (%) at 24 weeks
MAJORe HYPOGLYCEMIA
MINORf HYPOGLYCEMIA
Dapagliflozin 5 mg + metformin (n=137)
0
2 (1.5%)
Dapagliflozin 10 mg + metformin (n=135)
0
1 (0.7%)
Metformin monotherapy (n=137)
0
0


eMajor episodes of hypoglycemia were defined as symptomatic episodes requiring external (third-party) assistance due to severe impairment in consciousness or behavior with a capillary or plasma glucose value <54 mg/dL and prompt recovery after glucose or glucagon administration.

fMinor episodes of hypoglycemia were defined as either a symptomatic episode with a capillary or plasma glucose measurement <63 mg/dL, regardless of need for external assistance or an asymptomatic capillary or plasma glucose measurement <63 mg/dL that does not qualify as a major episode.

Use with Medications Known to Cause Hypoglycemia: Consider a lower dose of insulin and insulin secretagogues to reduce risk of hypoglycemia when coadministered with XIGDUO XR.

Hypoglycemia could occur when caloric intake is deficient, strenuous exercise is not compensated by caloric supplementation, or when XIGDUO XR is used with other glucose-lowering agents or ethanol.

STUDY DESIGN1,2

Dapagliflozin as Add-On Therapy to Metformin
Randomized, double-blind, placebo-controlled, multicenter, 24-week phase 3 trial
Metformin-treated A1C ≥7.0% and ≤10.0% (N=546)
Randomization
Dapagliflozin 5 mg (n=137)
Dapagliflozin 10 mg (n=135)
Dapagliflozin 2.5 mg (n=137)
Placebo (n=137)

Dapagliflozin 2.5 mg is not an FDA-approved dose; thus, data from this treatment group are not presented.

Study Objective

Evaluate the efficacy and safety of dapagliflozin in adult patients with type 2 diabetes who have inadequate glycemic control with metformin.

Primary End Point

Change in A1C from baseline at Week 24

Select Secondary End Point

  • Change in total body weight from baseline at Week 24

Other End Point

  • Change in seated systolic blood pressure at Week 24

Study Length

24 weeks

Key Inclusion Criteria

Patients were 18 to 77 years of age with type 2 diabetes who had an A1C level of ≥7.0% and ≤10.0%, body mass index (BMI) ≤45 kg/m2, fasting C-peptide ≥1.0 ng/mL, and were given a stable dose of metformin (≥1500 mg/day) for ≥8 weeks prior to enrollment. Patients with systolic blood pressure ≥180 mm Hg and/or diastolic blood pressure ≥110 mm Hg were excluded.

Study Dosing

Patients on metformin at a dose of at least 1500 mg per day were randomized after completing a 2-week, single-blind, placebo lead-in period. Following the lead-in period, eligible patients were randomized to dapagliflozin 2.5 mg, dapagliflozin 5 mg, dapagliflozin 10 mg, or placebo in addition to their current dose of metformin.

Dapagliflozin 2.5 mg is not an FDA-approved dose.