Insulin Degludec vs Glargine (Tresiba Vs Lantus)

Insulin Degludec Vs Glargine is a comparison of two long-acting insulins. They are the longer-acting insulins used commonly as basal insulins to provide insulin cover throughout the day. All insulins have the same mechanism of action.

Insulin is an anabolic hormone that regulates the metabolic pathways of carbohydrates, fats, and proteins.

Apart from carbohydrates, insulin also enhances the uptake of proteins and potassium into the cells. This post on Insulin Degludec vs Glargine (Tresiba Vs Lantus Insulin) is a review of the two insulins.

Which insulin is better, cheap, safe, effective in controlling blood glucose, and has a better cardiac safety profile?  

Drug Class: Insulin Degludec vs Glargine

• Insulin Degludec (Tresiba) is an ultra-long-acting insulin analog that has a slight structural variability compared to human insulin.
• Insulin Glargine (Lantus) is a long-acting insulin analog similar to insulin Degludec but has slight structural changes.

Concentrations and formulations available: Insulin Degludec vs Glargine

• Concentrations of Insulin available:

  • Insulin Degludec is available as U-100 and U-200. U-200 degludec is a concentrated form of U-100. One ml of U-200 contains 200 units. One ml of U-100 Degludec contains 100 units of insulin.
  • Insulin Glargine is available as U-100, U-300, and U-500. One ml of U-100, U-300, and U-500 contains 100, 300, and 500 units of insulin. Insulin Toujeo is the brand name of concentrated Insulin glargine.

• Combination with other anti-diabetic medications:

  • Insulin Glargine is available in combination with a GLP-1 analog, Lixesenatide, by the brand name Soliqua (100/33 units).
  • Insulin Degludec is available in combination with rapid-acting insulin (Insulin Aspart) by the brand name Insulin Ryzodeg

Duration and onset of action of Insulin Degludec and Glargine:

The onset of action of Insulin Degludec is about one hour. It has a half-life elimination of 25 to 36 hours depending on the dose.

Generally, it is considered peak-less insulin, the maximum concentration of the insulin Degludec is observed after 09 hours of its administration.

The Onset of action of insulin Glargine U-100 is about 3 – 4 hours and about 6 hours in the case of Glargine U-300 (Toujeo). It is peak-less insulin.

The duration of action of insulin glargine U-100 (Lantus Solostar) is 10.8 to 24 hours while that of insulin glargine U-300 (Toujeo Insulin) is more than 24 hours.

How to administer long-acting insulins (Insulin Degludec and Insulin Glargine)

Like all insulins, Insulin glargine and Degludec are administered subcutaneously. The preferred sites of injections are in the abdominal fat (slightly away from the umbilicus), thighs, and upper arms (the least preferred site except in very obese individuals).

Long and ultra-long-acting insulins can be administered at any time of the day. Insulin glargine U-100 is administered at a fixed time after dinner, Insulin Glargine U-300 (Toujeo) can be administered one to two hours before or after the scheduled time, while insulin Degludec can be administered at any time during the day.

Safety in Pregnancy and lactation:

Both insulin glargine and Degludec have not been studied in pregnancy. There is a potential for adverse fetal outcomes, however, pregnant patients with well-controlled blood glucose who are already on long-acting insulins can be continued on the same regimen.

Safety in kidney and liver diseases:

In patients with liver and kidney diseases, dosage adjustments have not been mentioned for both insulins. Strict glucose monitoring is required.

The preferred insulin regimens in these patients should be composed of short-acting insulins administered twice or thrice daily.

Tresiba vs Lantus Price Comparison:

Lantus & Toujeo:

• Insulin glargine U-100 costs per 100 units/ml: $34.03
• Insulin glargine U-300 costs per 300 units/ml: $103.66

Tresiba (Degludec):

• Insulin Degludec U-100 costs per 100 units/ml: $40.67
• Insulin Degludec U-200 costs per 200 units/ml: $81.35

Blood Glucose lowering effects of Degludec Vs Glargine (Tresiba Vs Lantus):

Insulin Degludec and Insulin Glargine (Tresiba and Lantus) are used as basal insulins. Both have been studied to reduce glycated hemoglobin effectively. Their efficacy in clinical trials has been comparable.

In one systemic review and meta-analysis, insulin Degludec was compared to insulin glargine in patients with T2DM. It was demonstrated that more participants in the Insulin Glargine group achieved the target HbA1C of less than 7% compared to Insulin Degludec.

However, this was achieved at the added risk of Hypoglycemia in the Insulin Glargine Group [Ref].

In the BEGIN (Clinical Development Program) program of Insulin Degludec that included three short exploratory trials and 9 therapeutic confirmatory trials, Insulin Degludec effectively reduced the blood glucose in both T1DM and T2DM across all age groups, ethnic groups, BMIs, and in combination with other antidiabetic medications.

The mean HbA1c decreased from 8.1 ± 0.8 % and 8.2 ± 0.8 % at baseline to 7.0 ± 0.9 % and 6.9 ± 0.8 % with Insulin Degludec and Insulin Glargine respectively after 104 weeks [Ref].

For individuals who required an insulin dose exceeding 60 units per day, both insulin glargine and Degludec were equally effective in lowering the HbA1C, however, the mean fasting glucose was lower in patients in the Degludec group compared to patients in the glargine group (115.4 mg/dL vs 119.8 mg/dL, P = .04) [Ref].

Tresiba Vs Lantus – Which Insulin causes more Weight gain:

All types of insulins can cause weight gain. This is specifically true for bolus insulins like Regular Insulin, Rapid-acting insulin analogs, and NPH insulin.

Basal Insulins like Detemir, Glargine, and Degludec Insulin causes less weight gain compared to bolus insulins.

One meta-analysis and systemic review compared Insulin Glargine and Insulin Degludec. There was no significant difference in weight gain between participants in either group (WMD 0.12, 95% CI – 0.19, 0.43, P = 0.46) [Ref].

In another review that evaluated the effect of Insulin Degludec and Insulin Glargine on body weight, it was concluded that there were no significant differences in the body weights in both type 1 DM and Type 2 DM.

The mean weight gain in T1DM with insulin Degludec was 1.79 Kg compared to 1.59 with Insulin Glargine at the end of the trial.

Similarly, In patients with T2DM, the increase in weight ranged from 1.29 to 3.61 kgs in patients who were administered Insulin Degludec while in individuals on Insulin Glargine, the gain in weight ranged from 1.41 to 3.97 kgs at the end of the trial period. The difference in the results was not statistically significant [Ref].

This was also demonstrated in a study comparing long-acting insulins’ efficacy and side effects. Weight gain occurred in both Insulin Glargine and Insulin Degludec, however, weight gain was significantly less with Insulin Detemir [Ref].

Which Insulin (Degludec vs Glargine) causes more hypoglycemia?

Insulin degludec and Insulin glargine are basal insulins. The risk of hypoglycemia with both these basal insulins is very less compared to the bolus insulins like Regular insulin, rapid-acting insulins (Insulin Aspart, Glulisine, Lyspro or Lispro), and NPH insulin.

However, compared to insulin glargine, the risk of hypoglycemia is much less with insulin Degludec compared to insulin glargine.

The risk of nocturnal hypoglycemia is specifically much lower with insulin Degludec. When administered at flexible intervals, the risk is further reduced compared to fixed-interval dosing.

Efficacy of Insulin Degludec Vs Glargine in Type 1 DM: Which Insulin is better:

Both Insulin Degludec and Insulin glargine is equally effective in patients with T1DM. The efficacy of insulin glargine and insulin Degludec in patients with T1DM is comparable.

However, the chances of hypoglycemia and nocturnal hypoglycemia in specific are much less with Insulin Degludec compared to Insulin Glargine.

This is demonstrated in the BEGIN Basal-Bolus Series of Clinical Trials. In the Begin Basal-Bolus T1DM Trial, both insulin Degludec and Insulin Glargine reduced the HbA1C from 7.7% at baseline to 7.4% and 7.5% at week 104 respectively.

These results were achieved with 12% less basal insulin and 9% overall less insulin requirements in the insulin Degludec group compared to patients in the insulin glargine group (P < .01).

Overall the risk of hypoglycemia was similar in both groups, however, the risks of nocturnal hypoglycemia were 25% lower in the insulin Degludec group [Ref].

Another study evaluated insulin Degludec administered in a fixed flexible dose i.e. administered at any time of the day compared to insulin Degludec and insulin administered at a fixed time in patients with T1DM.

The mean reduction in HbA1C was comparable, however, the mean total insulin, mean basal insulin, and the mean bolus insulin requirements were reduced by 11%, 4%, and 18% in patients treated with insulin Degludec.

The rates of nocturnal confirmed hypoglycemic episodes were much lower in Insulin Degludec administered at a flexible time compared to Insulin Degludec administered at a fixed time and insulin glargine.

There were 37% and 40% fewer hypoglycemic episodes in the insulin Degludec administered at a flexible time compared to fixed-interval Degludec and insulin glargine [Ref].

Cardiac Safety of Insulin Degludec vs Glargine:

This area is yet to be explored. However, some insights from a few studies are mentioned here.

The DEVOTE 7 Trial concluded that both insulins Deglduec and glargine were associated with increased cardiovascular deaths in patients aged 65 years or more, however, participants in the insulin Degludec had fewer episodes of hypoglycemia [Ref].

In a Danish cohort study, the risk of death was two-fold reduced in patients who were on insulin Degludec compared to insulin glargine (HR:0.54, 95% CI: 0.44-0.65), although, there were no significant differences in the incidence of major cardiovascular events [Ref].

In Conclusion:

Insulin Degludec and Insulin Glargine have comparable efficacies in both T1DM and T2DM. However, Insulin is ultra-long-acting insulin.

It has the advantage of flexible interval administration compared to insulin glargine.

The risk of hypoglycemia and nocturnal hypoglycemia in specific is much less with insulin Degludec compared to insulin glargine.