Dapagliflozin in type 2 diabetes: effectiveness across the spectrum of disease and over time.

Abstract

BACKGROUND:

Despite many available therapies, patients with type 2 diabetes mellitus (T2DM) frequently do not achieve/maintain glycaemic control. Furthermore, side effects such as hypoglycaemia and weight gain may limit therapy choices. Dapagliflozin, a selective sodium-glucose cotransporter-2 inhibitor, reduces hyperglycaemia by increasing glucosuria independently of insulin, representing a novel approach in T2DM. Dapagliflozin efficacy, safety and tolerability were evaluated across a wide range of clinical trials.

METHODS:

Dapagliflozin 10-mg efficacy data from (i) two short-term, active-comparator studies (vs. metformin-XR over 24 weeks and vs. glipizide over 52 weeks), (ii) pooled 24-week analyses of five placebo-controlled trials (as monotherapy or add-on therapy), and (iii) long-term studies over 2 years; dapagliflozin 5- and 10-mg pooled safety data from 12 placebo-controlled trials; and cardiovascular safety and malignancy data from 19 dapagliflozin studies were evaluated.

RESULTS:

In treatment-naïve patients (baseline HbA1c 9%), dapagliflozin reduced HbA1c (-1.45%) similarly to metformin-XR (-1.44%). In metformin-treated patients (baseline HbA1c 7.7%), dapagliflozin achieved a clinically significant reduction (-0.52%) similar to glipizide (-0.52%). In pooled 24-week analyses, dapagliflozin vs. placebo differences in HbA1c, weight and systolic blood pressure (SBP) were -0.60%, -1.61 kg and -3.6 mmHg, respectively. At 2 years, dapagliflozin vs. placebo differences in HbA1c and weight were -0.44 to -0.80% and -2.41 to -3.19 kg, respectively, and vs. glipizide, differences in HbA1c, weight, and SBP were -0.18%, -5.06 kg, and -3.89 mmHg, respectively. Major hypoglycaemia with dapagliflozin was rare (< 0.1%). Urinary tract and genital infections were more common with dapagliflozin, but responded to standard care and rarely led to study discontinuation. Events of renal failure/impairment and malignancies were rare and balanced across treatment groups. Pooled analyses did not indicate that dapagliflozin increased cardiovascular event risk.

CONCLUSIONS:

Dapagliflozin improved glycaemic control, decreased body weight, and lowered blood pressure across the spectrum of T2DM disease, with maintenance of these benefits over time.

• Authors: S Parikh, J Wilding, S Jabbour, E Hardy
• Journal: International journal of clinical practice (Int J Clin Pract) Vol. 69 Issue 2 Pg. 186-98 (Feb 2015) ISSN: 1742-1241 [Electronic] India
• PMID: 25438821 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons Ltd.

Chemical References

• Benzhydryl Compounds
• Blood Glucose
• Glucosides
• Glycated Hemoglobin A
• Hypoglycemic Agents
• dapagliflozin

Topics

• Adult
• Aged
• Benzhydryl Compounds (therapeutic use)
• Blood Glucose (drug effects)
• Body Weight (drug effects)
• Diabetes Mellitus, Type 2 (drug therapy)
• Double-Blind Method
• Female
• Glucosides (therapeutic use)
• Glycated Hemoglobin (drug effects)
• Humans
• Hypoglycemic Agents (administration & dosage, adverse effects, therapeutic use)
• Male
• Middle Aged
• Treatment Outcome
• Urinary Tract Infections (drug therapy)