For patients with diabetes, bringing down and maintaining lower blood glucose levels is important to minimize the risk of long-term complications such as nerve damage, kidney damage, an increased risk of heart disease, eye problems, and more.
Through a randomized, multicenter clinical trial sponsored by Novo Nordisk, investigators studied blood glucose results for patients assigned to either take insulin (insulin glargine, IGlar U100) or insulin degludec plus liraglutide (IDegLira), a combination of both insulin and an additional medication to help with blood sugar control.
The global study team found that participants who received IDegLira were better able to achieve blood glucose goals and remain at that goal longer compared to those assigned to receive IGlar.
Results are presented today at the American Diabetes Association’s Scientific Sessions and published simultaneously in The Lancet Diabetes & Endocrinology.
“We believe this reflects a more durable effect of IDegLira compared to IGlar, possibly related to the complementary roles and physiologic effects in the combination formulation,” said corresponding author and global signatory investigator Vanita R. Aroda, MD, a specialist in the Division of Endocrinology, Diabetes and Hypertension at Brigham and Women’s Hospital.
The study, known as DUAL VIII (Durability of insulin degludec plus liraglutide versus insulin glargine U100 as initial injectable therapy in type 2 diabetes) was a 104-week international, multicenter, open-label, phase 3b trial.
It enrolled 1,012 patients who were insulin-naïve, aged 18 and older, and had HbA1c 7-11% and a BMI of 20 kg/m² or higher on stable doses of oral antidiabetic drugs.
Patients were randomly assigned to take insulin glargine 100 units/mL (IGlar U100) or IDegLira, which contains a GLP-1 receptor analogue—a molecule that is similar to a naturally occurring compound that reduces blood glucose levels.
Both IDegLira and IGlar were administered as once-daily injections. The primary endpoint was time to need for treatment intensification.
Patients in the IDegLira group had significantly longer time until need for intensification of treatment than those in the IGlar group.
Investigators reported more effective glucose lowering, less weight gain and less risk of hypoglycemia, or low blood sugar, over the 104 weeks with the combination approach (IDegLira) compared to basal insulin alone (IGlar). No new safety or tolerability issues were reported in the trial.
In their paper, Aroda and her colleagues describe the clinical inertia that surrounds the treatment of diabetes.
Concerns about weight gain, low blood sugar and fear of injectables may prevent patients from achieving better glycemic control.
Although both IDegLira and IGlar were given as daily injections, IDegLira showed improved outcomes without the need for a separate, additional injection.
“IDegLira showed greater durability than IGlar U100 in reaching and maintaining patients at glycemic goals for longer, thereby minimizing the need for additional therapy, while also reducing the side effects often associated with insulin-only therapy,” the authors write.
“Taken together, the data from DUAL VIII illustrate the potential benefit of a combined insulin plus GLP-1RA approach, such as IDegLira, as a first injectable therapy.”
This study investigated the safety and efficacy of IDegLira as add-on to SGLT2i. In this 26-week, phase 3b, open-label trial, 420 patients with T2D uncontrolled on SGLT2i ± OADs were randomized 1:1 to receive add-on therapy of IDegLira or IGlar U100 (100 units [U]/mL).
Starting doses were 10 U in both treatment arms. Doses were titrated twice-weekly to a fasting glucose target of 72 to 90 mg/dL; only IDegLira had a maximum dose (50 U).
Mean A1C decreased from 8.2% at baseline to 6.3% at week 26 for IDegLira and from 8.4 to 6.7% for IGlar U100; IDegLira superiority confirmed (p<0.0001).
IDegLira treatment resulted in unchanged mean body weight vs. 2.0 kg weight gain with IGlar U100 (p<0.0001).
The rate of treatment emergent severe or blood glucose confirmed symptomatic hypoglycemic episodes was 58% lower (p=0.0035) with IDegLira (0.37 events/patient-year of exposure [PYE]) vs. IGlar U100 (0.90 events/PYE).
Total daily insulin dose after 26 weeks was 36 U for IDegLira vs. 54 U for IGlar U100 (p<0.0001).
Adverse event rates were low in both treatment arms with no unexpected safety issues.
In conclusion, superiority of IDegLira vs. IGlar U100 as add-on to SGLT2i was confirmed for glycemic control, body weight, hypoglycemia rate and total daily insulin dose.
Disclosure A. Philis-Tsimikas: Research Support; Self; Dexcom, Inc.. Advisory Panel; Self; Dexcom, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; Novo Nordisk A/S, Sanofi, Mylan. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. Employee; Spouse/Partner; Ionis Pharmaceuticals, Inc.. Stock/Shareholder; Spouse/Partner; Esperion Therapeutics, Ionis Pharmaceuticals, Inc.. Advisory Panel; Self; AstraZeneca. L. Billings: Advisory Panel; Self; Novo Nordisk A/S, Sanofi. Consultant; Self; Novo Nordisk A/S. Research Support; Self; Novo Nordisk A/S. Speaker’s Bureau; Self; Novo Nordisk A/S, Dexcom, Inc. R.S. Busch: Speaker’s Bureau; Self; AbbVie Inc., AstraZeneca. Research Support; Self; Bayer AG, Intarcia Therapeutics, Inc.. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Speaker’s Bureau; Self; Amgen Inc.. Research Support; Self; Sanofi US. Speaker’s Bureau; Self; Eli Lilly and Company, Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Amarin Corporation. C. Morales Portillo: Advisory Panel; Self; Novo Nordisk A/S, Sanofi, Eli Lilly and Company, Boehringer Ingelheim GmbH, Merck Sharp & Dohme Corp., Janssen Pharmaceuticals, Inc., AstraZeneca, Abbott. Research Support; Self; Novo Nordisk A/S, Sanofi, Eli Lilly and Company, Boehringer Ingelheim GmbH, Merck Sharp & Dohme Corp., Janssen Pharmaceuticals, Inc., AstraZeneca, Theracos, Inc., Lexicon Pharmaceuticals, Inc.. Speaker’s Bureau; Self; Novo Nordisk A/S, Sanofi, Eli Lilly and Company, Boehringer Ingelheim GmbH, Merck Sharp & Dohme Corp., Janssen Pharmaceuticals, Inc., AstraZeneca, Abbott. R. Sahay: Advisory Panel; Self; Boehringer Ingelheim, Sanofi, Eli Lilly and Company, Novo Nordisk A/S. Advisory Panel; Spouse/Partner; Intas Pharmaceuticals Ltd., Pfizer Inc.. Speaker’s Bureau; Self; Sanofi, Eli Lilly and Company, Boehringer Ingelheim, Dr. Reddys Laboratories, USV Private Limited, Glenmark. Speaker’s Bureau; Spouse/Partner; Boehringer Ingelheim. N. Halladin:Employee; Self; Novo Nordisk A/S. R. Juhl: Employee; Self; Novo Nordisk A/S. S. Harris: Advisory Panel; Self; Novo Nordisk A/S, Sanofi, Merck, AstraZeneca, Amgen Inc., Lilly/Boehringer Ingelheim, Abbott, Janssen. Consultant; Self; Novo Nordisk A/S, Sanofi, Merck, AstraZeneca, Lilly/Boehringer Ingelheim, Abbott, Janssen. Research Support; Self; Novo Nordisk A/S, Sanofi, Merck, Abbott, AstraZeneca, Janssen. Other Relationship; Self; CIHR, CDA, The Lawson Foundation.
- by the American Diabetes Association.
More information: Vanita R Aroda et al. Durability of insulin degludec plus liraglutide versus insulin glargine U100 as initial injectable therapy in type 2 diabetes (DUAL VIII): a multicentre, open-label, phase 3b, randomised controlled trial, The Lancet Diabetes & Endocrinology (2019). DOI: 10.1016/S2213-8587(19)30184-6
Journal information: The Lancet Diabetes & Endocrinology
Provided by Brigham and Women’s Hospital
