Meeting News CoveragePerspective

Insulin glargine bested sitagliptin for HbA1c reduction in insulin-naïve type 2 diabetes

PHILADELPHIA - Patients with poorly controlled type 2 diabetes who were administered basal insulin in addition to metformin experienced significant improvements in HbA1c, according to data presented by Pablo Aschner, MD.

In a comparative, parallel, randomized, open-label trial included 515 patients with type 2 diabetes aged 35 to 70 years who had been treated with metformin for at least 3 months and had an HbA1c of 7% to 11% and a BMI of 25 to 45 were recruited from 17 countries. They were randomly assigned to a 24-week add-on treatment with insulin glargine (n=250) or sitagliptin (n=265).

Aschner, who is associate professor of endocrinology at the Javeriana University School of Medicine, and and director of research at the San Ignacio University Hospital in Bogotá, Colombia, and colleagues designed the Evaluation of insulin glargine versus Sitagliptin in Insulin-naïve patients (EASIE) trial to determine the efficacy, safety and tolerability of basal insulin (insulin glargine) compared with a DPP-4 inhibitor (sitagliptin).

Insulin glargine was titrated from an initial subcutaneous dose of 0.2 units per kg of patients’ body weight to achieve a fasting plasma glucose of 4.0 mmol/L to 5.5 mmol/L; sitagliptin 100 mg was administered once daily by mouth.

“Insulin glargine was 1.6 times more likely than sitagliptin to achieve an HbA1c under 7% and 2.5 times more likely to achieve HbA1c less than 6.5%,” Aschner said during his presentation. The results were simultaneously published in The Lancet.

Reduction in HbA1c was significant for patients on insulin glargine (–1.72%) vs. those on sitigliptin (–1.13%), with a mean difference of –0.59% (P≤.0001). However, the rate of symptomatic hypoglycemic events was eight times greater with insulin glargine (4.21 events per patient-year) compared with sitagliptin (0.5 events per patient-year; P<.001).

“The risk of severe events was low and severe nocturnal hypoglycemia was the same for both groups. These results are in agreement with other randomized clinical trials. Insulin glargine in other trials has reduced HbA1c by 1.7% or more, as we found in EASIE,” Aschner said.

“Another striking finding was that patients’ weight on insulin increased by only a mean of 0.44 kg, although the final dose had increased to 0.5 U/kg of body weight. Usually insulin therapy is associated with considerable weight gain. With sitagliptin patients lost a mean of 1.08 kg, which was also unexpected since DPP-4 inhibitors are considered weight-neutral,” Aschner told Endocrine Today.

In an accompanying editorial, Michaela Diamant, MD, associate professor of endocrinology and scientific director of the Diabetes Centre at VU University Medical Centre in The Netherlands, said the study confirms that proper dosage of basal insulin added to metformin is effective in lowering HbA1c. However, Diamant wrote that long-term efficacy is unknown.

“At present, it is unclear whether initiation of basal insulin in the early stage of type 2 diabetes translates into longer term outcome benefits or whether its early use is ultimately offset by progressive weight gain and more hypoglycaemic events, both of which could result in increased cardiovascular risk, higher cost and poor quality of life,” he wrote. – by Samantha Costa

For more information:

Aschner P. Joint ADA/The Lancet Symposium. Presented at: the American Diabetes Association’s 72nd Scientific Sessions; June 8-12, 2012; Philadelphia.

Aschner P. Lancet. 2012; doi: 10.10.1016/S0140-6736(12)60439-5.

Diamant M. Lancet. 2012; doi: 10.1016/S0140-6736(12)60780-6.

Disclosure: Dr. Aschner has served on advisory boards for AstraZeneca, Eli Lilly and Company, GlaxoSmithKline, Janssen, Merck, Sharpe & Dohme, Novartis, and Sanofi and speaker’s bureaus for AstraZeneca, Eli Lilly and Company, Merck, Sharpe & Dohme, Novartis, and Sanofi. Other researchers report similar disclosures, which can be found on the cited study.

PHILADELPHIA - Patients with poorly controlled type 2 diabetes who were administered basal insulin in addition to metformin experienced significant improvements in HbA1c, according to data presented by Pablo Aschner, MD.

In a comparative, parallel, randomized, open-label trial included 515 patients with type 2 diabetes aged 35 to 70 years who had been treated with metformin for at least 3 months and had an HbA1c of 7% to 11% and a BMI of 25 to 45 were recruited from 17 countries. They were randomly assigned to a 24-week add-on treatment with insulin glargine (n=250) or sitagliptin (n=265).

Aschner, who is associate professor of endocrinology at the Javeriana University School of Medicine, and and director of research at the San Ignacio University Hospital in Bogotá, Colombia, and colleagues designed the Evaluation of insulin glargine versus Sitagliptin in Insulin-naïve patients (EASIE) trial to determine the efficacy, safety and tolerability of basal insulin (insulin glargine) compared with a DPP-4 inhibitor (sitagliptin).

Insulin glargine was titrated from an initial subcutaneous dose of 0.2 units per kg of patients’ body weight to achieve a fasting plasma glucose of 4.0 mmol/L to 5.5 mmol/L; sitagliptin 100 mg was administered once daily by mouth.

“Insulin glargine was 1.6 times more likely than sitagliptin to achieve an HbA1c under 7% and 2.5 times more likely to achieve HbA1c less than 6.5%,” Aschner said during his presentation. The results were simultaneously published in The Lancet.

Reduction in HbA1c was significant for patients on insulin glargine (–1.72%) vs. those on sitigliptin (–1.13%), with a mean difference of –0.59% (P≤.0001). However, the rate of symptomatic hypoglycemic events was eight times greater with insulin glargine (4.21 events per patient-year) compared with sitagliptin (0.5 events per patient-year; P<.001).

“The risk of severe events was low and severe nocturnal hypoglycemia was the same for both groups. These results are in agreement with other randomized clinical trials. Insulin glargine in other trials has reduced HbA1c by 1.7% or more, as we found in EASIE,” Aschner said.

“Another striking finding was that patients’ weight on insulin increased by only a mean of 0.44 kg, although the final dose had increased to 0.5 U/kg of body weight. Usually insulin therapy is associated with considerable weight gain. With sitagliptin patients lost a mean of 1.08 kg, which was also unexpected since DPP-4 inhibitors are considered weight-neutral,” Aschner told Endocrine Today.

In an accompanying editorial, Michaela Diamant, MD, associate professor of endocrinology and scientific director of the Diabetes Centre at VU University Medical Centre in The Netherlands, said the study confirms that proper dosage of basal insulin added to metformin is effective in lowering HbA1c. However, Diamant wrote that long-term efficacy is unknown.

“At present, it is unclear whether initiation of basal insulin in the early stage of type 2 diabetes translates into longer term outcome benefits or whether its early use is ultimately offset by progressive weight gain and more hypoglycaemic events, both of which could result in increased cardiovascular risk, higher cost and poor quality of life,” he wrote. – by Samantha Costa

For more information:

Aschner P. Joint ADA/The Lancet Symposium. Presented at: the American Diabetes Association’s 72nd Scientific Sessions; June 8-12, 2012; Philadelphia.

Aschner P. Lancet. 2012; doi: 10.10.1016/S0140-6736(12)60439-5.

Diamant M. Lancet. 2012; doi: 10.1016/S0140-6736(12)60780-6.

Disclosure: Dr. Aschner has served on advisory boards for AstraZeneca, Eli Lilly and Company, GlaxoSmithKline, Janssen, Merck, Sharpe & Dohme, Novartis, and Sanofi and speaker’s bureaus for AstraZeneca, Eli Lilly and Company, Merck, Sharpe & Dohme, Novartis, and Sanofi. Other researchers report similar disclosures, which can be found on the cited study.

    Perspective
    M. Sue Kirkman

    M. Sue Kirkman

    One important aspect of this study is that after metformin, which is the typical initial therapy for type 2 diabetes, we really do not have a lot of strong evidence of what to do next. I know it seems like all therapies may be pretty much the same as far as the published evidence, so there is a need to have more head-to-head comparisons of different therapies for second-line therapy. I think one of the issues is that people are reluctant to use insulin and, clearly, I think a lot of patients and maybe even a lot of health care professionals find it easier to prescribe another pill. Another interesting aspect of this study is that it did show that with a relatively simple insulin regimen, glycemic control really was better. I thought it was also interesting that not only was fasting glucose lower but even postprandial glucose was lower. You would think that the DPP-4 inhibitor might have performed better than a basal insulin there. But, at least in people who are fairly early in the course of diabetes really do respond very well to insulin therapy with a simple once-daily regimen with a low risk of hypoglycemia.

    • M. Sue Kirkman, MD
    • Senior Vice President of Medical Affairs and Community Information American Diabetes Association

    Disclosures: Dr. Kirkman reports no relevant financial disclosures.

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