Subscribe

Diabetes Drug Pipeline: Promising Agents in Late Stages of Development

Value-Based Care in Cardiometabolic Health August 2012, Vol 1, No 2 - Emerging Therapies
Wayne Kuznar

A number of promising oral and injectable agents for diabetes are currently in late-stage development and were featured in posters, oral abstract presentations, and symposia during the 2012 ADA annual meeting. The following is a sampling of new medications with potentially important implications for the treatment of patients with diabetes.

Lixisenatide is an injectable glucagon- like peptide-1 (GLP-1) receptor agonist currently in phase 3 clinical trials; in the multinational GetGoal-P study, lixisenatide was able to lower hemoglobin (Hb) A1c levels further in patients with type 2 diabetes who were already being treated with pioglitazone, with or without metformin, but who had failed to achieve glycemic control with pioglitazone, with or without metformin (here).

The news was mixed regarding albiglutide, because this GLP-1 receptor agonist, currently in phase 3 clinical trials, was noninferior to insulin lispro in achieving glycemic control in patients with type 2 diabetes who were not adequately controlled with insulin; however, albiglutide was not able to demonstrate noninferiority on this end point in a comparative trial versus liraglutide.

Several sodium glucose cotransporter (SGLT)-2 inhibitors are in late-stage development. Canagliflozin is an SGLT-2 inhibitor that was superior to glimepiride and to sitagliptin in lowering HbA1c levels in 2 separate phase 3 clinical studies of patients with type 2 diabetes in whom metformin, with or without a sulfonylurea, failed to achieve glycemic control.

Another investigational SGLT-2 inhibitor, empagliflozin, which is currently in phase 2b clinical trials, showed sustained reductions in average HbA1c levels for up to 90 weeks in patients with type 2 diabetes when used as monotherapy or as an add-on to metformin. Furthermore, empagliflozin was associated with significant reductions in fasting plasma glucose (FPG) and excess body weight (here).

A third SGLT-2 inhibitor, dapag­liflozin, improved glycemic control in 2 clinical trials in patients with type 2 diabetes, cardiovascular (CV) disease, and hypertension. Dapagliflozin had no effect on CV safety. Another study showed no renal toxicity with dapag­liflozin. In addition, dapagli­flozin demonstrated a long-term (up to 104 weeks) reduction in HbA1c levels in patients with type 2 diabetes and poor glycemic control despite previously receiving high doses of insulin.

Ipragliflozin is yet another SGLT-2 inhibitor in phase 3 clinical trials. In a 24-week, placebo-controlled, randomized study of 168 patients with type 2 diabetes who were receiving a constant metformin dose for at least 12 weeks before being randomized, ipragliflozin therapy lowered HbA1c levels by 1.3% compared with placebo. Significant reductions in FPG and blood pressure levels were also seen with ipragliflozin.

Imeglimin is the first in a new, tetrahydrotriazine-containing class of oral antidiabetes agents—the glimins. In a 12-week, multicenter, phase 2 clinical trial, imeglimin was shown to be effective as add-on therapy to metformin in reducing HbA1c levels and FPG in patients with type 2 diabetes.

The ultra–long-acting insulin degludec was as effective as insulin glargine in terms of glycemic control in patients with type 2 diabetes. Furthermore, insulin degludec resulted in lower rates of severe hypoglycemia and nocturnal hypoglycemia than insulin glargine. The pharmacokinetic profile of insulin degludec suggests an effect in excess of 24 hours and low variability in subcutaneous absorption (here).

The long-acting basal insulin LY2605541 performed well compared with insulin glargine in studies of patients with type 1 or type 2 diabetes, with mean reductions in HbA1c of 0.6% with LY2605541 versus 0.4% with insulin glargine. Of note, LY2605541 also was associated with weight reduction (here).

Related Items
Tumor-Infiltrating Lymphocyte Therapy Induces Responses Across Wide Range of Patients with Advanced Melanoma
Wayne Kuznar
August 2020 Vol 13, Special Issue published on August 17, 2020 in Emerging Therapies
Intratumoral Injection of Cisplatin and Vinblastine, with or without Pembrolizumab, Improves Intracellular Transport in Patients with Advanced Solid Tumors
Chase Doyle
August 2020 Vol 13, Special Issue published on August 17, 2020 in Emerging Therapies
The WEE1 Inhibitor Adavosertib Displays Promising Clinical Activity in Uterine Serous Cancer
Wayne Kuznar
August 2020 Vol 13, Special Issue published on August 17, 2020 in Emerging Therapies
Mosunetuzumab, a Dual-Targeted Antibody, Shows Complete Remissions in Relapsed/Refractory NHL After CAR T-Cell Therapy
Phoebe Starr
February 2020 Vol 13, Special Issue published on February 25, 2020 in Emerging Therapies
Apamistamab-Based Lymphodepleting Regimen Before CAR T-Cell Therapy May Prevent Cytokine Release Syndrome
Wayne Kuznar
February 2020 Vol 13, Special Issue published on February 25, 2020 in Emerging Therapies
Last modified: September 26, 2012
Copyright © Engage Healthcare Communications, LLC. All rights reserved.