Dulaglutide as a Substitute for Long-Acting Insulin in a Basal-Bolus Regimen?

Summary and Comment |
June 18, 2015

Dulaglutide as a Substitute for Long-Acting Insulin in a Basal-Bolus Regimen?

  1. Bruce Soloway, MD

Blood glucose was controlled a little better but at the cost of more adverse events.

  1. Bruce Soloway, MD

When type 2 diabetes is difficult to control, clinicians often resort to basal-bolus insulin regimens. Could the long-acting basal insulin in such a regimen be replaced by a long-acting glucagon-like peptide-1 (GLP-1) agonist, perhaps conferring lower risk for hypoglycemia?

Dulaglutide (Trulicity) is a GLP-1 agonist that was approved by the FDA in 2014 for once-weekly injection. In a manufacturer-conducted study, researchers randomized 884 adults with glycosylated hemoglobin (HbA1c) levels ≥7.0%, despite fixed insulin doses once or twice daily, to receive weekly dulaglutide (0.75 or 1.5 mg) or daily bedtime insulin glargine (Lantus). All patients received thrice-daily prandial insulin lispro (Humalog). Participants were allowed to take metformin but no other oral diabetes medications. Glargine and lispro doses were titrated by algorithm to achieve fasting and preprandial blood glucose levels of 71 to 99 mg/dL. Treatment assignments were not concealed, except for dose of dulaglutide.

After 26 weeks, adjusted mean declines in HbA1c levels were significantly greater with high- and low-dose dulaglutide than with glargine (−1.64%, −1.59%, and −1.41%, respectively), and significantly more patients who received high- or low-dose dulaglutide than patients who received glargine reached the HbA1c target of <7.0% (68%, 69%, and 57%, respectively). Gastrointestinal side effects were significantly more common with dulaglutide than with glargine, and the incidence of symptomatic hypoglycemia was about 80% in all three groups.

Comment

Substitution of a long-acting GLP-1 agonist for long-acting insulin in a regimen that also includes aggressively titrated prandial insulin boluses might improve overall glycemic control slightly, but the incidence of hypoglycemia remains high, and gastrointestinal adverse effects occur frequently.

Editor Disclosures at Time of Publication

  • Disclosures for Bruce Soloway, MD at time of publication Nothing to disclose

Citation(s):

Reader Comments (6)

Adalberto Fernandez Physician, Cardiology, BEST

I agree with the James Dale´comment

GAURANGA DHAR Physician, Family Medicine/General Practice, Dhaka, Bangladesh

Very good approach. In addition to less hypoglycemia, combination of GLP-1 agonist and basal insulin will be convenient for a patient for dose titration compared to combination of meal time bolus insulin and GLP-1 agonist.

Hani Shalabi Fellow-In-Training, Endocrinology

I think replacing long acting insulin by long acting GLP-1 is misconception , the glucose-dependent effect of GLP-1 will benefit postprandial plasma glucose control and that explain the hypoglycemia when combined with short acting insulin .it will be more appropriate to combined GLP -1with basal insulin which was proven in many studies to have better control and less hypoglycemia.

GAURANGA DHAR Physician, Family Medicine/General Practice, Dhaka, Bangladesh

Both advantages and disadvantages. Patients with dulaglutide will receive 6 shots less compared to glargine group per week. Weight benefit will be observed in dulaglutide group but treatment cost will be higher in this group. Although according to number of recent studies, GLP-1 agonists are found safe in terms of both acute and chronic pancreatitis but still we can not ignore it in practice. Research also found that use of GLP-1 agonists may be associated with C-cell hyperplasia, the precursor of thyroid medullary carcinoma.

CARLOS-EDUARDO GIRALDO Physician Physician, Hospital San Vicente de Paul Caldas -Colombia

Promising results, in terms of HBA1C control treatment with dulaglutide shows a better result compared to conventional basal bolus scheme with glargine and lispro but, better improvement in HBA1C by itself does not mean better diabetic control, some issues must be analyzed: Adherence and comorbidities needs an aditional approach.
In terms of adherence Dulaglutide shows some problems: nausea, vomiting and dyspepsia are determinants at the moment of evaluate adherence, adherence depends almost exclusively on the patients, a good labor as physicians support the initial decision of the patient but finally, the choice of take or not to take the prescribed medications relies on the patients and for many patients this decision is based on its cultural mental design; in this specific case Dulaglutide has a big challenge to solve before to become a recomended drug in the management of refractory diabetes mellitus type 2.
Refractory DM II implies a lot of faces, one of them: Comorbidities, many patients had DM II and hypertension or dislipidemia or Hypothyroidism or a mixture of all those illneses, it would be interesting to know in this study how was the configuration of the comorbidities and how those illnesses affect the outcomes, residual confusion can be standing behind the results, confusion is inevitable during the investigation, is not a mistake if you take it into account , but not to declare it is as harmfull as a study with bias. During the investigation the author centered de discussion around the glycaemic control according to the objectives proposed it, but forgot the resisual confusion, so discussion about comorbidities needs to be done.
Finally the Diabetes Mellitus control needs a multidisciplinary approach and cannot be reduced just to reduce HBA1C, an important outcome in this study would be improvement in cardiovascular disease and the reduction in cardiovascular mortality, probably this two points could support and reinforce the conclusion but without it Dulaglutide has no choice if compared with conventional insulin scheme, I really think that this investigation shows promising results and I invite the author to continue proving new choices. For the moment these results must be analyzed with caution.

James Dale

I have found using GLP-1 inhibitor in place of prandial short acting insulin to be beneficial when used with metformin and a basal bedtime insulin titrated to control fasting AM glucose.

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