May Combos Substitute Basal-Bolus Insulin in Kind 2 Diabetes?

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For patients with type 2 diabetes who receive multiple daily insulin injections, switching to combination treatment with basal insulin plus one of two newer glucose-lowering drug classes may be a more convenient and safer alternative, a new randomized study shows.

The study shows that switching patients from basal bolus insulin (BBI) (four injections per day) to either a fixed combination of basal insulin plus either a glucagon-like peptide-1 receptor agonist (GLP-1 Agonists) or a daily oral sodium-glucose cotransporter-2 inhibitor (SGLT2 inhibitor) resulted in comparable blood glucose control, but with lower insulin doses, fewer injections, and less hypoglycemia.

The progressive loss of beta cell function in patients with type 2 diabetes often requires the use of insulin. About a quarter of people with type 2 diabetes are currently receiving insulin therapy, but only 50% of those people reach a target A1c of <7%. The American Diabetes Association advises considering intensification of injectable insulin therapy when the basal dose is >0.5 units / kg / day and A1c remain above target.

The new data, however, “appear to refute the dogma of the intangibility of the BBI regimen in type 2 diabetes by providing evidence that it is possible and safe to switch from a BBI regimen to either a once-daily fixed-dose combination or once.” daily switching gliflozin pill added to basal insulin, “say Dr. Dario Giugliano of the University of Campania, Naples, Italy and colleagues in their article published online in Diabetes Care on April 21st.

“This simplification strategy can work for a significant and clinically relevant reduction in A1c in many patients who have maintained their results for at least 6 months,” they note, “and the addition of a drug with proven cardiorenal benefits can be considered as such. ” another potential benefit of the combination strategy. “

If the results are continued beyond the 6 month period of the study, Giugliano and colleagues say, “They will facilitate the role of the physician, appreciate the patient, and hopefully give practitioners better guidance in the choice of medication.”

“Really important work”: approach could combat “overbasing”

Rozalina G. McCoy, MD, an endocrinologist and family doctor at the Mayo Clinic in Rochester, Minnesota, described the study as “really important work.”

She told Medscape Medical News that she frequently sees patients on basal insulin, but instead of early insulin, their basal dose has been continually increased to the point of “overbasing” that doesn’t cover the foods they eat, but it can also lead to hypoglycemia.

“So if we keep going up the basal that’s a problem, but it’s either too much basal or they’re on a complex regimen of four injections a day,” she said.

In contrast, she said, “I think this study really shows that if we use either GLP-1 agonists or SGLT2 inhibitors with basal insulin, we can effectively meet some of our food needs without the hypoglycemia, the weight gain, and the treatment burden of MDI [multiple daily injection] Therapy.”

However, she noted, “This is a short study, only 6 months. The big question is how much time do we buy? Many patients with type 2 diabetes will end up needing multiple daily insulin injection therapies, but the hope and where I think I this study is coming in to delay that as much as possible. “

Equivalent glucose lowering, fewer injections, less hypoglycemia

The study included 305 adults over 35 years of age with type 2 diabetes whose A1c levels were> 7.5% with basal bolus injection therapy lasting several days (four injections per day).

They were randomly given either an intensification of their current basal bolus regimen, a fixed combination of basal insulin plus a GLP-1 agonist (IDegLira or IGlarLixi) or basal insulin plus SGLT2 inhibitor (either canagliflozin, dapagliflozin, or empagliflozin). . Of the 305 patients, 100%, 88% and 91% completed the study, respectively.

The primary result, changes in A1c from baseline at 6 months, were -0.6, -0.6 and -0.7 percentage points (P = 0.356) for BBI, the GLP-1 agonist combination and the SGLT2 inhibitor -Combination. The proportion of patients who achieved A1c values ​​of ≤7.0%, ≤7.5% and ≤8.0% did not differ significantly between the three groups (P = 0.189), with both combinations compared to the basal bolus were not inferior (P <) .001 for both).

Total daily insulin doses increased in the basal bolus group and decreased in both combination groups (superiority, P <0.01 for both). Patients in the fixed GLP-1 agonist combination group showed a significant weight loss compared to the other two groups (-1.9 kg versus -0.6 kg for the SGLT2 inhibitor combination and an increase of 0.3 kg with BBI; P <0.001, P =. 855 or P = 0.159).

The proportions of at least one episode of Stage 1 hypoglycemia (<70 mg / dL with symptoms / signs) were 17.8%, 7.8% and 5.9% for basal bolus, fixed GLP-1 agonists -Combination or SGLT2 inhibitor combination (P = 0.015). Less than 5% of patients in a group had grade 2 (<54 mg / dL) or level 3 (<50 mg / dL or require assistance) hypoglycemia.

Approach could help avoid therapeutic indolence in primary care

McCoy said she doesn’t typically use fixed-dose basal insulin-GLP-1 agonist combination products because they don’t offer as much flexibility as giving the drugs separately. “You don’t get as much use as possible with fixed combos because there is so much you can give,” she said.

However, she said, “The principle of basal insulin plus GLP-1 agonist or SGLT2 inhibitor is really important as it will, if at all, help avoid this impasse of basal insulin therapy in primary care.”

“It is really difficult for the primary care provider to start MDI therapy. It takes a lot of patient education and close monitoring. Hopefully this will help with some of these therapeutic inertias.”

The study was funded in part by the Associazione “Salute con Stile” in Naples, Italy. Giugliano has received honoraria for speaking at meetings from Novartis, Sanofi, Eli Lilly and Company, AstraZeneca, and Novo Nordisk. McCoy is funded by the National Institutes of Health.

Diabetes treatment. Published online April 21, 2021. Executive summary

Miriam E. Tucker is a freelance journalist based out of Washington, DC. She writes regularly for Medscape. Her work has appeared in the Washington Post, NPR’s Shots blog, and Diabetes Forecast magazine. She can be found on Twitter @MiriamETucker.

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