Forxiga DEPICT-1 trial demonstrates improved glycaemic control without increasing hypoglycaemia, lowered weight and total daily insulin dose in patients with type-1 diabetes



First Phase III trial of a selective sodium glucose cotransporter-2 (SGLT-2) inhibitor as oral adjunct to insulin in type-1 diabetes (T1D)

Overall adverse event profile was in line with known clinical profile of dapagliflozin, with no imbalance in adverse events reported

DEPICT-1 24-week results presented at the European Association for the Study of Diabetes (EASD) and simultaneously published in The Lancet Diabetes & Endocrinology

 

14 September 2017

AstraZeneca today announced 24-week results from the DEPICT-1 (Dapagliflozin Evaluation in Patients With Inadequately Controlled Type 1 Diabetes) trial, the first Phase III trial of a selective SGLT-2 inhibitor, Forxiga (dapagliflozin), as an oral adjunct to insulin in T1D. These data were presented at the 53rd Annual Meeting of the EASD and simultaneously published in The Lancet Diabetes and Endocrinology.

The trial showed that dapagliflozin, when given as an oral adjunct to adjustable insulin in patients with inadequately-controlled T1D, demonstrated significant and clinically-relevant reductions from baseline in HbA1c, weight reductions, and lowered total daily insulin dose at 24 weeks compared to placebo at both the 5 mg and 10 mg dose.1

Analysis1

HbA1c*

Body weight (Body Mass Index/BMI)*

Total daily insulin dose*

Dapagliflozin 5 mg + Insulin vs. Placebo + Insulin

-0.42%

(95% CI, -0.56,              -0.28; p<0.0001)

-2.96%

(95% CI, -3.63, -2.28; p<0.0001)

-8.8%

(95% CI, -12.6, -4.9; p<0.0001)

Dapagliflozin 10 mg + Insulin vs. Placebo + Insulin

-0.45%

(95% CI, -0.58,              -0.31; p<0.0001)

-3.72%

(95% CI, -4.38, -3.05, p<0.0001)

-13.2%

(95% CI, -16.8, -9.4; p<0.0001)

*Mean change from baseline to week 24; CI = Confidence Interval

Further, as assessed by continuous glucose monitoring (CGM), treatment with dapagliflozin at both doses reduced mean glucose and glucose fluctuations (assessed by mean amplitude of glycaemic excursions) and increased the percentage of glucose readings in the target range (70-180mg/dL). Specifically, patients treated with dapagliflozin 5 mg and 10 mg spent more than 2 hours and more than 2.5 hours longer in target glucose range each day, respectively.1

The overall adverse event profile is in line with the known clinical profile of dapagliflozin, with no imbalance in adverse events reported. Occurrence of hypoglycaemia overall, as well as severe hypoglycaemia, were not increased in the dapagliflozin treatment groups compared with placebo. Similarly, dapagliflozin was not associated with an increase in the occurrence of definite diabetic ketoacidosis (DKA) compared with placebo. Four (1%) events occurred in the dapagliflozin 5 mg group, five (2%) occurred in the dapagliflozin 10 mg group and three (1%) occurred in the placebo group, respectively. Insulin pump failure and missed insulin doses were the most frequent risk factors for definite DKA in the placebo and dapagliflozin groups.1

Paresh Dandona, MD, PhD, Distinguished Professor of Medicine and Chief of the Division of Endocrinology, Diabetes and Metabolism, University of Buffalo and lead investigator of the DEPICT-1 trial, said: “There remains a high unmet medical need in helping treat the millions of patients living with type-1 diabetes while managing the complications associated with the disease. It is critical that we continue to advance clinical research with newer and novel therapies. The 24-week results from DEPICT-1 are important as they represent the first Phase III trial in type-1 diabetes of the newer selective SGLT-2 class of diabetes medicines as an oral adjunct to insulin. Our results suggest that dapagliflozin is a potential adjunct treatment to insulin to significantly improve glycaemic control in patients with type-1 diabetes.”

Elisabeth Björk, Vice President, Head of Cardiovascular and Metabolic Diseases, Global Medicines Development, AstraZeneca, said: “We are excited about the initial results from the DEPICT programme. Being able to improve glucose control without increasing the risk of hypoglycaemia targets an unmet medical need in type-1 diabetes. Investigating the needs of new patient groups within diabetes is in line with our patient-centric approach to exploring the broader clinical impact of dapagliflozin.”

Dapagliflozin is not currently licensed for use in type-1 diabetes.

 

NOTES TO EDITORS

About the DEPICT Clinical Programme

The DEPICT clinical programme consists of two clinical trials, DEPICT-1 (NCT02268214)2 and DEPICT-2 (NCT02460978)3. DEPICT-1 and DEPICT-2 are 24-week, randomised, double-blind, parallel-controlled trial designed to assess the effects of dapagliflozin 5 mg or 10 mg on glycaemic control in patients with type-1 diabetes inadequately controlled by insulin. All patients will be evaluated at week 24 and after a 28-week extension (52 weeks total).Error! Bookmark not defined.,2,3

About AstraZeneca in Cardiovascular, Renal & Metabolic Diseases (CVMD)

Cardiovascular, renal and metabolic diseases are key areas of focus for AstraZeneca as the company sets the challenge to better understand how its portfolio of medicines might be used to help address multiple risk factors or co-morbidities across CVMD. Today, AstraZeneca is delivering life-changing results in the core CV disease areas and their complications. AstraZeneca is investing in the science to demonstrate CV and mortality benefits by slowing the underlying progression of CV-related disease and protecting the organs of the CV system. Ultimately, AstraZeneca is looking to do more than just slow CV-related disease, but to modify or even halt the natural course of the disease itself and regenerate organs. The net result is a strong, continued commitment to new CVMD treatment options that have the potential to deliver improved outcomes to hundreds of millions of patients across the globe.

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular & Metabolic Diseases and Respiratory. The Company also is selectively active in the areas of autoimmunity, neuroscience and infection. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. 

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References

  1. Dandona P, Mathieu C, Phillip M, et al. Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (DEPICT-1): 24-week results from a randomised controlled trial. Lancet Diabetes and Endocrinol. http://dx.doi.org/10.1016/PII. Published Online September 14, 2017.
  2. National Institutes of Health. Dapagliflozin evaluation in patients with inadequately controlled type 1 diabetes (DEPICT 1). ClinicalTrials.gov website. http://clinicaltrials.gov/show/NCT02268214. Accessed July 30, 2017.
  3. National Institutes of Health. Dapagliflozin evaluation in patients with inadequately controlled type 1 diabetes (DEPICT 2). ClinicalTrials.gov website. http://clinicaltrials.gov/show/NCT02460978. Accessed July 30, 2017.