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

SAFETY PROFILE

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ANALYSIS OF ADVERSE REACTIONS

Established tolerability profile in a 24-week study of treatment-naïve patients

Most commonly reported adverse reactions (≥5% and more commonly than with placebo)1,a

PERCENTAGE OF PATIENTS

IN TREATMENT-NAÏVE STUDYa,b Saxagliptin 5 mg + metformin IR Placebo + metformin IR
Headache 7.5% 5.2%
Nasopharyngitis 6.9% 4.0%
  (n=320) (n=328)

aMetformin IR was initiated at a starting dose of 500 mg and titrated up to a maximum of 2000 mg daily.

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

  • There was a dose-related mean decrease in absolute lymphocyte count observed with saxagliptin1
  • Incidence of diarrhea was 6.9% with saxagliptin 5 mg + metformin IR vs 7.3% with placebo + metformin IR over 24 weeks1,2
  • A total of 2.5% in the saxagliptin 5 mg + metformin IR group and 3.4% in the placebo + metformin IR group discontinued due to adverse events over 24 weeks2

Adverse reactions in placebo-controlled monotherapy trials of metformin XR occurring in >5% of metformin XR-treated patients and more commonly than in placebo-treated patients1 

PERCENTAGE OF PATIENTS

  Metformin XR Placebo
Diarrhea 9.6% 2.6%
Nausea/Vomiting 6.5% 1.5%
  • Diarrhea led to discontinuation of study medication in 0.6% of the patients treated with metformin extended-release1

Pooled analysis of adverse reactions occurring in ≥5% of patients treated with saxagliptin 5 mg and more commonly than in patients treated with placebo1,c

Overall incidence of adverse events with saxagliptin in monotherapy and add-on therapy studies was similar to placebo, 72% vs 71%, respectively.1

PERCENTAGE OF PATIENTS

IN MONOTHERAPY AND ADD-ON THERAPY STUDIESc Saxagliptin 5 mg Placebo
Upper Respiratory Tract Infection 7.7% 7.6%
Urinary Tract Infection 6.8% 6.1%
Headache 6.5% 5.9%
  (n=882) (n=799)
  • In patients treated with saxagliptin 2.5 mg, headache (6.5%) was the only adverse reaction occurring in ≥5% of patients and more commonly than placebo1
  • Adverse reactions reported in ≥2% of patients treated with saxagliptin 5 mg or saxagliptin 2.5 mg and ≥1% more frequently compared with placebo, respectively, included:

    - Sinusitis: 2.6%, 2.9% vs 1.6%

    - Abdominal pain: 1.7%, 2.4% vs 0.5%

    - Gastroenteritis: 2.3%, 1.9% vs 0.9%

    - Vomiting: 2.3%, 2.2% vs 1.3%

  • Hypersensitivity-related events (eg, urticaria, facial edema) were reported in 1.5%, 1.5%, and 0.4% of patients who received saxagliptin 5 mg, 2.5 mg, and placebo, respectively1
  • There was a dose-related mean decrease in absolute lymphocyte count observed with saxagliptin1

cPrespecified pooled analysis of 2 monotherapy studies, the add-on to metformin study, the add-on to glyburide study, and the add-on to a TZD study; 24-week data regardless of glycemic rescue.

Most common adverse events associated with discontinuation of therapy over 6 months1,d

Discontinuation of therapy due to adverse events occurred in 3.3%, 2.2%, and 1.8% of patients receiving saxagliptin 5 mg, 2.5 mg, and placebo, respectively.1

PERCENTAGE OF PATIENTS

  Saxagliptin 5 mg Saxagliptin 2.5 mg Placebo
Lymphopenia 0.5% 0.1% 0.0%
Rash 0.3% 0.2% 0.3%
Blood Creatinine Increase 0.0% 0.3% 0.0%
Blood Creatine Phosphokinase Increase 0.2% 0.1% 0.0%
  (n=882) (n=882) (n=799)

dReported in at least 2 patients treated with saxagliptin.

In the clinical trial database for saxagliptin to date, there have been 6 reports (0.12%) of tuberculosis among the patients treated with saxagliptin compared with no reports among the patients treated with comparator. Causality has not been established. In addition, 1 patient treated with saxagliptin developed suspected foodborne fatal salmonella sepsis. There have been no spontaneous reports of tuberculosis or opportunistic infections associated with saxagliptin use.

INCIDENCE OF HYPOGLYCEMIC EVENTS

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

Saxagliptin 5 mg + metformin IR (n=320)

Placebo + metformin IR (n=328)

eReported 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.

  • In a pool of 5 placebo-controlled trials, the most common adverse reactions reported in ≥5% of patients treated with saxagliptin 5 mg vs placebo were upper respiratory tract infection (7.7%, 7.6%), urinary tract infection (6.8%, 6.1%), and headache (6.5%, 5.9%)1
  • In other pivotal clinical trials of pooled data, in patients treated with ONGLYZA 2.5 mg, headache (6.5%) was the only adverse reaction occurring in ≥5% of patients and more commonly than in patients treated with placebo1

     

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.

Saxagliptin 5 mg add-on therapy to metformin + sulfonylurea

Incidence of hypoglycemic events at Week 241,4

Reported hypoglycemia: Saxagliptin 5 mg + metformin + sulfonylurea (10.1%), Placebo + metformin + sulfonylurea (6.3%)  Confirmed Hypoglycemia:  Saxagliptin 2.5 mg + metformin + sulfonylurea (1.6%), Placebo + metformin + sulfonylurea (0%)
Reported hypoglycemia: Saxagliptin 5 mg + metformin + sulfonylurea (10.1%), Placebo + metformin + sulfonylurea (6.3%)  Confirmed Hypoglycemia:  Saxagliptin 2.5 mg + metformin + sulfonylurea (1.6%), Placebo + metformin + sulfonylurea (0%)

fAdverse reactions of hypoglycemia were based on all reports of hypoglycemia.

gDefined as symptoms of hypoglycemia accompanied by a fingerstick glucose ≤50 mg/dL.


GI EVENTS

Incidence of diarrhea over 24 weeks2,3,h

PERCENTAGE OF PATIENTS

  Saxagliptin 5 mg + metformin IR Saxagliptin 2.5 mg + metformin IR Placebo + metformin IR
Uncontrolled on Metformin Monotherapy 5.8% 9.9% 11.2%
  (n=191) (n=192) (n=179)
Treatment-Naïvei 6.9% -- 7.3%
  (n=320)   (n=328)

hIn these studies, saxagliptin and metformin IR were administered as separate tablets.

iMetformin IR was initiated at a starting dose of 500 mg and titrated up to a maximum of 2000 mg daily.

  • In both studies, mean decrease in body weight from baseline to Week 24 with KOMBIGLYZE XR was similar to that of metformin IR alone1,2