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A TREATMENT FOR ADULTS WITH TYPE 2 DIABETES MELLITUS, IN ADDITION TO DIET AND EXERCISE

INITIAL DRUG THERAPY

Demonstrated significant reductions in A1C levels and lower rates of hypoglycemia, in treatment-naïve patients

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START WITH SIGNIFICANCE

A ONCE-DAILY TABLET THAT CAN HELP GET PATIENTS TO GOAL1

PRIMARY END POINT

Patients taking saxagliptin 5 mg + metformin IR achieved a 2.5% mean A1C reduction from baseline vs 2.0% mean A1C reduction from baseline with placebo + metformin IR1,2,a

Adjusted mean change in A1C baseline for Saxagliptin 5 mg + metformin IR (-2.5%) vs Placebo + metformin IR in treatment-naïve patients (-2.0%)
Adjusted mean change in A1C baseline for Saxagliptin 5 mg + metformin IR (-2.5%) vs Placebo + metformin IR in treatment-naïve patients (-2.0%)

P<0.0001 vs metformin IR + placebo.

aLeast squares mean adjusted for baseline value.

  • The proportion of patients who discontinued for lack of glycemic control or who were rescued for meeting prespecified glycemic criteria on metformin IR alone vs saxagliptin 5 mg + metformin IR was 10.1% vs 7.5%, respectively2

A statistically significant number of treatment-naïve patients reached A1C goal of <7.0% at 24 weeks1,2,b-d

SECONDARY END POINT

of patients taking saxagliptin 5 mg + metformin immediate-release (IR) (n=307) achieved A1C <7.0% vs 41% taking placebo + metformin IR (n=314); P<0.05 vs placebo + metformin IR. Mean baseline A1C of 9.4% for both groups1,2,e

bIntent-to-treat population using last observation on study or last observation prior to pioglitazone rescue therapy for patients needing rescue.

cIn this study, saxagliptin 5 mg and metformin IR were administered as separate tablets. Mean daily metformin IR doses at Week 24 were 1790 mg for saxagliptin 5 mg + metformin IR and 1817 mg for placebo + metformin IR.2

dP<0.05 vs placebo + metformin.

eLeast squares mean adjusted for baseline value.

LOWER RATES OF REPORTED HYPOGLYCEMIA OVER 24 WEEKS1,2,f

3.4% of patients reported lower rates of hypoglycemia over 24 weeks with Saxagliptin 5 mg + metformin IR vs 4.0% of patients that were given Placebo + metformin IR
3.4% of patients reported lower rates of hypoglycemia over 24 weeks with Saxagliptin 5 mg + metformin IR vs 4.0% of patients that were given Placebo + metformin IR

In this study, saxagliptin 5 mg and metformin IR were administered as separate tablets.

fReported hypoglycemic events were a combination of reports of either signs or symptoms consistent with hypoglycemia with or without documented glucose levels or reported low glucose levels without symptoms. A concurrent glucose measurement was not required or was normal in some patients. Therefore, it is not possible to conclusively determine that all these reports reflect true hypoglycemia.

Hypoglycemia: When saxagliptin was used in combination with a sulfonylurea or with insulin, the incidence of confirmed hypoglycemia was increased over that of placebo. Consider lowering the dose of these agents when coadministered with KOMBIGLYZE XR.

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


SIGNIFICANT REDUCTIONS IN FPG AND PPG1,2

Saxagliptin 5 mg + metformin IR as initial combination therapy with metformin IR delivered statistically significant reductions in fasting plasma glucose (FPG) and postprandial glucose (PPG) vs placebo + metformin IR at 6 months1,2,g,h

FPG: Saxagliptin 5 mg + metformin IR (-60mg/dL) vs Placebo + metformin IR (-47mg/dL). 2-hr PPG: Saxagliptin 5 mg + metformin IR (-138mg/dl) vs Placebo + metformin IR (-97mg/dl)

P<0.05 vs placebo + metformin IR.

GREATER REDUCTIONS WITH SAXAGLIPTIN 5 MG + METFORMIN IR

FPG

-13 mg/dL

(95% Cl: -19 mg/dL, -6 mg/dL)

2-HOUR PPG

-41 mg/dL

(95% Cl: -57 mg/dL, -25 mg/dL)

FPG: Saxagliptin 5 mg + metformin IR (-60mg/dL) vs Placebo + metformin IR (-47mg/dL). 2-hr PPG: Saxagliptin 5 mg + metformin IR (-138mg/dl) vs Placebo + metformin IR (-97mg/dl)

P<0.05 vs placebo + metformin IR.

GREATER REDUCTIONS WITH SAXAGLIPTIN 5 MG + METFORMIN IR

-13 mg/dL

(95% Cl: -19 mg/dL, -6 mg/dL)

FPG: Saxagliptin 5 mg + metformin IR (-60mg/dL) vs Placebo + metformin IR (-47mg/dL). 2-hr PPG: Saxagliptin 5 mg + metformin IR (-138mg/dl) vs Placebo + metformin IR (-97mg/dl)

P<0.05 vs placebo + metformin IR.

GREATER REDUCTIONS WITH SAXAGLIPTIN 5 MG + METFORMIN IR

-41 mg/dL

(95% Cl: -57 mg/dL, -25 mg/dL)

gIn these studies, saxagliptin 5 mg and metformin IR were administered as separate tablets.

hIntent-to-treat population using last observation on study prior to pioglitazone rescue therapy for patients needing rescue.


STUDY DESIGN1,2

Initial Drug Therapy

Phase 3, multicenter, international, randomized, double-blind, active-controlled study

Treatment-naïve A1C ≥8.0% and ≤12.0% (N=1306)

Randomization: Saxagliptin 5 mg + metformin IR (n=320), Saxagliptin 10 mg  + metformin (n=323), Saxagliptin 10 mg  + placebo (n=335), Metformin IR + placebo (n=328)
Randomization: Saxagliptin 5 mg + metformin IR (n=320), Saxagliptin 10 mg  + metformin (n=323), Saxagliptin 10 mg  + placebo (n=335), Metformin IR + placebo (n=328)

Study Objective

Evaluate the efficacy and safety of saxagliptin as initial combination therapy with metformin IR, in addition to diet and exercise, compared to metformin IR monotherapy in treatment-naïve patients.

Primary Efficacy End Point

A1C change from baseline at 6 months

Secondary Efficacy End Points Included

  • FPG change from baseline at 6 months
  • Percentage of patients achieving A1C <7.0%
  • PPG change from baseline following an oral glucose tolerance test at 6 months

Study Length

6 months

Study Length

6 months

 

Key Inclusion Criteria

Key Inclusion Criteria

Demographic: Men and women age 18–77 years; patients had to be treatment-naïve

Diagnosis: Type 2 diabetes mellitus (T2DM)

A1C: ≥8.0% and ≤12.0%

Fasting C-peptide: ≥1.0 ng/mL

Body Mass Index: ≤40 kg/m2

 

Study Dosing

Study Dosing

  • Saxagliptin 5 mg  + metformin IR 500 mg*
  • Saxagliptin 10 mg  + metformin IR 500 mg*
  • Saxagliptin 10 mg  + placebo
  • Metformin IR 500 mg* + placebo

*Metformin IR dose was between 1000 and 2000 mg daily. Metformin IR was initiated at a starting dose of 500 mg daily, up-titrated to 1000 mg at Week 1, and thereafter up-titrated as tolerated to a maximum of 2000 mg daily based on FPG through Week 5.

Primary Efficacy End Point

A1C change from baseline at 6 months

Secondary Efficacy End Points Included

  • FPG change from baseline at 6 months
  • Percentage of patients achieving A1C <7.0%
  • PPG change from baseline following an oral glucose tolerance test at 6 months

*Metformin IR dose was between 1000 and 2000 mg daily. Metformin IR was initiated at a starting dose of 500 mg daily, up-titrated to 1000 mg at Week 1, and thereafter up-titrated as tolerated to a maximum of 2000 mg daily based on FPG through Week 5.

Primary Efficacy End Point

A1C change from baseline at 6 months

Secondary Efficacy End Points Included

  • FPG change from baseline at 6 months
  • Percentage of patients achieving A1C <7.0%
  • PPG change from baseline following an oral glucose tolerance test at 6 months

*Metformin IR dose was between 1000 and 2000 mg daily. Metformin IR was initiated at a starting dose of 500 mg daily, up-titrated to 1000 mg at Week 1, and thereafter up-titrated as tolerated to a maximum of 2000 mg daily based on FPG through Week 5.