Comparison of 6 HARMONY trials showed that albiglutide not only treats type 2 diabetes as effectively as current methods but may reduce the burden felt by other injection-based treatments.
Patients with type 2 diabetes (T2D) have shown positive clinical outcomes equivalent to that of other treatments with the use of once-weekly albiglutide (Tanzeum), according to data from GlaxoSmithKline’s HARMONY 1-6 trials.
In addition to assisting patients with T2D achieve better glycemic control, the international research teams working on the series of studies found that patients using albiglutide were less likely to require rescue therapy, had lower incidents of hypoglycemic events, saw increased weight loss (in comparison to other treatment regimens), and remained rescue free longer than those patients receiving alternative therapies.
Two recent studies revealed albiglutide's potential for treating T2D and highlight the associated benefits of albiglutide use as a stand-alone or combination treatment.
Philip D. Home, PhD, MRCP, DM, MBBCh, and colleagues from the UK, US, Sweden, and Germany, examined data from the first 5 HARMONY studies to determine efficacy, durability, tolerance, and safety after 3 years of treatment, in the first study. Their analysis determined that albiglutide provided durable glycemic control and that most study patients remained rescue-free for 2 to 3 years.
The second, led by Lawrence A. Leiter, MD, (pictured) with St. Michael's Hospital at the University of Toronto in Canada, and international colleagues with the HARMONY 6 study group, released results of the 52-week HARMONY 6 randomized, open-label, multicenter, phase 3 trial comparing once-weekly use of albiglutide to thrice-daily use of prandial insulin lispro for controlling insulin in adult patients with T2D.
While albiglutide and insulin lispro were equally effective in reducing baseline hemoglobin A1C (HbA1c) in adult patients with T2D, study participants treated with albiglutide saw increased weight loss and lower incidents of symptomatic hypoglycemia than those treated with insulin lispro.
The study also found that although albiglutide had a higher incidence of gastrointestinal (GI) adverse reactions than insulin lispro, the adverse events reported were equal to or less than those found with other GLP 1RA treatments.
The HARMONY trials involved more than 5,000 patients in 11 countries. The first 2 trials—both 52-week, randomized, double-blind, placebo-controlled studies—determined that albiglutide as an add-on therapy (HARMONY 1) or a standalone therapy (HARMONY 2) was effective in lowering HbA1c, signaling lower average glycemic levels and greater diabetic control. The article by Home and colleagues reported that over 60% of participants taking albiglutide achieved HbA1c of <7.0% after treatment, with an average of -0.70% reduction in baseline HbA1c levels.
HARMONY 3 (104-weeks) tested it as an add-on to metformin and determined that the addition of the drug allowed patients to achieve a significant reduction in baseline HbA1c (an average of -0.78%), allowing HARMONY 4 (52-weeks) to test the combination of the two against basal insulin.
The comparison showed that although patients on both medications achieved a similar reduction in baseline HbA1c, patients taking albiglutide plus metformin saw significant weight loss during the 52-week trial, averaging -1.1 kg in comparison with patients using basal insulin treatments who saw an average weight increase of +1.6 kg.
HARMONY 5 compared albiglutide as an add-on therapy with metformin against other metformin add-ons, finding that although the use of albiglutide was equivalent to other medications in controlling diabetes, patients experienced significantly more weight loss with the use of albiglutide. Patients receiving albiglutide averaged a loss of 0.7 kb per 26 weeks in comparison to a gain of 0.8 kb with the use of insulin lispro.
Among cases with observed data at the 3-year time point, albiglutide treatment also resulted in lower HbA1c of <7.0% in both the rescue-free and all-participants groups in 33 to 60% of participants. The majority of participants (avg. 63.4%) randomized to albiglutide did not require rescue therapy within 2 years, and in some cases, did not require rescue within the 3-year study duration. Median time to hyperglycemic rescue was greater than 118 weeks in HARMONY 2, and longer than 107 and 138 weeks in HARMONY 4 and 5.
HARMONY 6 compared albiglutide to insulin lispro as an add-on/combination therapy with insulin glargine in patients with T2D. The 52-week trial (with 8-week follow-up) showed that there was a non-significant (-0.2%) difference between reductions in HbA1c levels in the 2 groups.
Patients receiving albiglutide and insulin glargine (n=285) saw a 0.82% reduction in HbA1c levels at 26 weeks and a 1.01% reduction at 52 weeks, while patients receiving insulin lispro and insulin glargine (n=281) saw a 0.66% reduction in HbA1c levels at 26 weeks and a .097% reduction at 52 weeks. There was also a reported non-significant difference between patients in the two groups requiring hyperglycemic rescue during the 52-week study (42.6% of albiglutide patients to 38.8% of insulin lispro patients).
Leiter and colleagues with the HARMONY 6 group remarked that though there was no statistically significant difference between the effectiveness of either medication on the primary endpoint goal of lowering HbA1c levels in patients, there was a statistically significant difference in other areas of note.
Patients receiving albiglutide saw a reduction in body weight from baseline during the 52-week study, with an average weight loss of 0.96 kg (2.12 lbs) versus an average weight gain of 1.66 kg (3.66 lbs) among those patients receiving insulin lispro. Leiter reports that there was also a reduced likelihood of on-therapy hypoglycemia events for patients receiving albiglutide (32.6%) versus insulin lispro (49.8%).
In addition to reporting study results, Home, Leiter, and fellow HARMONY researchers made a point to note the potential for albiglutide to reduce the patient burden associated with treatment regimens in their separate studies.
Home and colleagues argued that one of the burdens of T2D is polypharmacy and that the use of multiple, sometimes shifting medications, to address the disease and associated morbidities while maintaining glycemic control is important. If albiglutide can provide stable glycemic control for patients with T2D, it would circumvent the need for additional rescue medication and lift some of the polypharmacy burdens.
Home wrote that “deteriorating glycaemic control mandates stepped addition and changes in therapy with injectable agents--which in the past mainly meant insulin therapy--is often required.” He further stated that use of albiglutide can offer assistance with durable glycemic control and that its use as a stand-alone or add-on treatment for T2D appears to provide opportunities for clinicians to optimize management of glycaemia for long-term patient benefit.
Leiter and the HARMONY 6 group also pointed out the potential for albiglutide to lessen treatment burden, noting that the simpler regimen of once-weekly albiglutide versus the standard 21-injection weekly regimen required with insulin lispro would drastically reduce patient burden and may increase patient adherence to treatment for T2D.
Data from Leiter and the HARMONY 6 group did show that patients receiving albiglutide had an increased incidence of gastrointestinal adverse events (41.8% of patients reporting GI adverse events with albiglutide) versus insulin lispro (21.4%) but that only 1.4% of patients with GI adverse events withdrew from treatment due to symptoms.
Leiter told MD Magazine that the GI effects were "relative to other GLP 1RAs" such as exenatide (Byetta or Bydureon/AstraZeneca) and dulaglutide (Trulicity/Eli Lilly), and that although patients on albiglutide had a higher incidence of GI adverse events, "these were generally transient and rarely led to treatment discontinuation. In fact, albiglutide appears to have a lower incidence of GI adverse events relative to the other GLP1RA."