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Once-Daily Insulin More Convenient But No More Effective Then Multiple Injections of Lispro

Apr 8, 2008

Once-daily injections of insulin glargine (Lantus) may control type 2 diabetes as well as multiple injections of insulin lispro (Humalog) and reduce side effects at the same time, researchers found.

Basal insulin therapy had a similar effect on  A1c levels as prandial insulin (1.7% versus 1.9% reduction) but yielded 78% fewer hypoglycemic events, less weight gain, and greater patient satisfaction, reported Thomas Linn, M.D., Ph.D., of Justus Liebig University Giessen, and colleagues in the March 29 issue of The Lancet.

"Insulin glargine provides a simple and effective option that is more satisfactory to patients than is lispro for early initiation of insulin therapy," they wrote.

The findings also help address the ongoing debate over whether to target therapy to fasting glucose or postprandial glucose, said Yogish C. Kudva, M.B.B.S., and Victor M. Montori, M.D., of the Mayo Clinic in Rochester, Minn., in an accompanying editorial.

But the issue will not be settled until studies link improvements to outcomes that matter to patients, such as diabetes complications, Drs. Kudva and Montori said.

The APOLLO (A Parallel design comparing an Oral antidiabetic drug combination therapy with either Lantus once daily or Lispro at mealtime in type 2 diabetes patients failing Oral treatment) was a non-inferiority study funded and done by the makers of the basal insulin under evaluation.

It included 205 type 2 diabetes patients randomly assigned to open-label insulin glargine once daily at the same time every day and 210 patients randomized to insulin lispro three times daily before meals.

All the patients had A1c concentrations between 7.5% and 10.5% and fasting blood glucose concentrations of 6.7 mmol/L or more despite being on stable doses of oral antidiabetic agents.  Most patients in both groups remained on metformin (74% to 76%) and glimepiride (Amaryl, 93% to 94%) throughout the trial. After 44 weeks of treatment, mean A1c decreased from 8.7% to 7.0% in the insulin glargine group and from 8.7% to 6.8% in the insulin lispro group (P<0.0001 for both).

Despite the debate about whether fasting or postprandial blood glucose concentrations have a greater effect on A1c, the researchers said, "our data suggest that the reduction of A1c is more dependent on targeted insulin therapy per se rather than on a specific glucose profile."

As expected, though, insulin glargine reduced nocturnal blood glucose and morning fasting glucose better whereas postprandial glucose levels were better with insulin lispro.

More patients in the insulin lispro group than in the insulin glargine group reached hemoglobin A1c targets, including:

  • 7% or less (69% versus 57%)
  • 6.5% to 7% (30% versus 27%)
  • Less than 6.5% (38% versus 30%)

But more patients reached target fasting blood glucose concentrations of 5.5 mmol/L or less with insulin glargine than with insulin lispro by the end of the study (35% versus 5% in the intent-to-treat analysis, P<0.0001).  Insulin lispro better controlled postprandial blood glucose throughout the day (P<0.0001).  Hypoglycemia events were substantially less common with insulin glargine than with insulin lispro (4.27 versus 19.46 per patient, P<0.0001), although severe events were not significantly different between groups.

Weight gain from baseline tended to be lower with insulin glargine (3.01 versus 3.54 kg, P=0.23).

While patients in both groups reported a fairly high level of satisfaction with treatment, insulin glargine-treated patients had significantly greater increases in satisfaction than lispro-treated patients (P<0.0001). Notably, satisfaction scores related to convenience of treatment worsened in the lispro group compared with baseline but improved in the glargine group.

These advantages for insulin glargine may help poorly controlled patients accept making a timely shift from oral agents alone to the addition of insulin, the researchers conclude

Practice Pearl:
Explain to interested patients that the study found no difference in effect on glycosylated hemoglobin A1c between the two types of insulin, although once-daily injections may be more convenient and improve some outcomes.
Bretzel RG, et al "Once-daily basal insulin glargine versus thrice-daily prandial insulin lispro in people with type 2 diabetes on oral hypoglycemia agents (APOLLO): An open randomized controlled trial" Lancet 2008; 371: 1073-84.

Kudva YC, Montori VM "Patient-centered treatments for type 2 diabetes" Lancet 2008; 371: 1047-48.


Red Wine, Tea, Helps Regulate Blood Sugar in Type 2’s: Food scientists have found that certain antioxidants found in red wine and tea may help regulate the blood sugar of people with type 2 diabetes by inhibiting the action of alpha-glucosidase that controls the absorption of glucose from the small intestine, and protect the body from complications such as high blood pressure and heart disease.  See This Weeks’ Item #15