Grace Halsey

The GLP-1 receptor agonist liraglutide used to treat patients with type 2 diabetes (T2D) for 26 weeks had no impact on bone resorption, even though subjects lost weight.

Liraglutide treatment also appeared to preserve hip bone mineral density vs placebo. Study findings were published online ahead of print on December 20 in the journal 

"Liraglutide treatment for 26 weeks did not affect bone resorption and preserved hip BMD despite weight loss in patients with T2D, suggesting that liraglutide has some antiresorptive effect," the authors wrote.

Liraglutide is approved to reduce hyperglycemia in adults with T2D and also has been shown in  animal studies to affect bone turnover by decreasing bone resorption. Writing in the background to the study, authors, led by Katrine Hygum, a doctoral student in the department of endocrinology and internal medicine at Aarhus University Hospital in Denmark, point to a reduction in bone turnover in patients with T2D that may be a result of changes in bone signaling and hyperglycemia.

The researchers note that the postprandial incretin response is reduced in T2D patients and that “incretin hormones may also affect bone turnover, but a direct effect of GLP-1 on osteoblasts is controversial.”

In the randomized double-blind clinical trial, 60 adults with T2D were assigned to treatment with liraglutide 1.8 mg daily or placebo for 26 weeks. The primary endpoint was change in p-collagen 1 cross-linked C-terminal telopeptide (p-CTX). P-CTX is a highly responsive marker of bone resorption, the magnitude of which study investigators expected to see decline.

BMD was assessed at the total hip, femoral neck, and lumbar spine at baseline, 13 weeks, and 26 weeks via DXA. Bone microarchitecture, geometry, and estimated strength also were measured at those points at the right-side radius and tibia via quantitative computed tomography.

Among patients treated with liraglutide, CTX increased by 0.07 µg/L (95% CI, 0.03-0.1) and among patients treated with placebo by 0.03 µg/L (95% CI, 0-0.06). Changes were not different between the 2 groups.

Subjects in the liraglutide group lost weight from baseline to week 4 (P <.001) that was sustained thereafter.

Procollagen type 1 N-terminal propeptide (P1NP), the most sensitive biomarker of bone formation decreased among patients treated with liraglutide from baseline to week 4 (P <.01) but increased between weeks 4 and 13 (P =.03) and remained elevated thereafter.

Weight and P1NP did not change among patients treated with placebo.

The authors conclude that the absence of effect of on bone resorption, and the preservation of BMD despite weight loss among T2D patients treated with liraglutide suggests that the GLP-1 receptor agonist may have some antiresorptive effect.

Limitations of the study include the small sample size and while all patients had T2D, not all had an indication for liraglutide and so were not necessarily representative of patients treated in real-world settings.

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Dipeptidyl peptidase-4 inhibitors (DPP-4Is) have been in the type 2 diabetes tool box since 2006. They are associated with a modest decrease in A1c and a mostly neutral impact on weight. There are currently four approved agents in the US and there are also five approved agents that combine a DPP-4I with metformin and one that combines a DPP-4I and a thiazolidinedione.

How well versed are you in the language of DPP-4I? Find out in 5 short questions.

1. Which one of the following DPP-4I combination drugs does NOT contain metformin: 

Please click here for answer and next question. 

2. The DPP-4I combination drug that contains a thiazolidinedione is: 

Oseni combines alogliptin and pioglitazone; Nesina is alogliptin; Trulicity is dulaglutide; Onglyza is saxagliptin

Kazano combines metformin with which of the following DPP-4Is? 

4. Januvia is the brand name for which of the following generic DPP-4Is? 

5. Jentadueto is the brand name for the combination of saxagliptin and metformin. 

Please click here for answer and table of all drugs mentioned

Table. DPP-4Is, DPP-4I Combinations, GLP-1 Receptor Agonists

There are 10 FDA-approved DPP-4 inhibitors--single agents and combination products. Do you speak their language? Find out with these 5 questions. 

Do You Speak DPP-4I? 

1. Canagliflozin is the generic name for:

2. Xigduo combines which of the following antihyperglycemic agents:

3. Which of the following SGLT2 inhibitors goes by the trade name Farxiga?

4. When you combine linagliptin and empagliflozin, you get:

5. The trade name Jardiance refers to which of the following?  

One for good measure. The trade name of the drug that combines metformin and dapagliflozin is:

5 correct: A+  You've been paying attention!

2 correct: D    Start carrying a laminated cheat sheet 

1 correct: F     Nearby P & T notified 

0 corrrect:      Remedial pharmacy tutoring for you!

Trade names often mask the essential nature of a medication, but some of the new agents that treat type 2 diabetes take it to a new level. Here, 5 chances to see what you know. 

Diabetes Drug Quiz: Do You Know Your Generics vs Trades? 

Since June of 2014, the US FDA has approved a number of drugs for a variety of endocrine-related disease, including 3 sodium glucose cotransporter 2 inhibitors for the treatment of type 2 diabetes. These plus 7 more make an even 10 that you may be interested in.

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Since June of 2014, the US FDA has approved a number of drugs for a variety of endocrine-related diseases. Here are 10 of them. 

Author | Grace Halsey

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Liraglutide May Increase Bone Strength, Study Shows

Do You Speak DPP-4I?

Diabetes Drug Quiz: Do You Know Your Generics vs Trades?

10 New FDA-Approved Endocrinology Drugs