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.

Articles

Liraglutide May Increase Bone Strength, Study Shows

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. 

10 New FDA-Approved Endocrinology Drugs 

Guidelines recently published by The Endocrine Society stress the importance of aggressive management of obesity before tackling the host of comorbidities commonly associated with the disease including diabetes, hypertension, and dyslipidemia. The guidelines were 

published online in the Journal of Clinical Endocrinology and Metabolism 

The first guideline of its kind, the collected recommendations focus on the appropriate and most effective use of the numerous medications now available to treat overweight and obesity. Lead guideline author Caroline Apovian, MD, of Boston University, notes that existing guidelines from The Obesity Society (TOS), the American Heart Association (AHA), and the American College of Cardiology (ACC) cover management of obesity through lifestyle, diet and exercise, and surgery. Anti-obesity drugs are mentioned but little guidance is provided. At the time each of these guidelines was published ,there were very few agents available and so a dearth of randomized clinical trials on which to base recommendations.

Describing the new guideline as a "blueprint" on the medical management of obesity, Apovian explains it also takes into account the 

 and that the task force she heads stands by national recommendations for management of overweight and obese patients.

There are 6 FDA-approved drugs for the treatment of obesity, 4 of them approved during the past 2 years: lorcaserin (Belviq, Eisai), phentermine/topiramate (Qsymia, Vivus), naltrexone/bupropion (Contrave, Takeda), and liraglutide (Saxenda, Novo Nordisk). Orlistat 160 mg (Xenical, Glaxo Smith Kline) and orlistat OTC (alli, Glaxo Smith Kline) have been available since 2007.

The guideline stresses that use of pharmacologic therapy in no way lessens the role of the essential components of obesity management-diet, exercise, and behavioral modifications. Maintenance of weight loss over time depends on incorporating durable lifestyle changes in these domains.

The current requirements for using FDA-approved weight loss medications include a BMI of 27 with at least one weight-related comorbidity (eg, diabetes, hypertension) or a BMI of 30 or more.

The guideline’s recommended treatment strategies are based on a shift toward managing obesity more aggressively as a primary disease rather than “waiting” until complications ensue and then tackling much larger and multifactorial metabolic dysfunction.

For eligible patients who elect to include anti-obesity medications in a weight-loss program, Dr Apovian emphasizes the importance of regular, face-to-face visits. The Centers for Medicare and Medicaid Services (CMS) covers 15 visits per year as of this writing.

 Continue medication in patients who respond well and lose at least 5% of their body weight after 3 months. Poor efficacy or significant adverse effects should trigger a switch to other medications and/or therapeutic strategies.

 For overweight or obese patients with diabetes, prescribe medications that promote weight loss or are weight-neutral; metformin remains first-line. Consider adding a GLP-1 agonist, then SGLT2 inhibitor before sulfonylureas or insulin.

 Limit potential for weight gain in obese patients with hypertension and diabetes by using ACE inhibitors, ARBs, and CCBs for first-line treatment

For patients who need medications associated with weight gain (eg, antidepressants, antipsychotics, antiepileptic drugs) provide full disclosure and estimates of anticipated effect on weight for each option; decision making should be shared by patient and provider.

Phentermine and diethylpropion should not be used in patients with uncontrolled hypertension or history of heart disease.

Apovian CM, Aronne JL, Bessesen JH, et al. Pharmacological management of obesity: an endocrine society clinical practice guidline. 

Jensen MD, Ryan DH, Donato KA, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. 

. 2013. Published online before print November 12, 2013. 

The new guidelines signal a shift toward aggressive treatment for obesity as a primary disease and following with treatment for comorbidites that do not respond to weight loss. 

Lead With Weight Loss, Say New Endo Society Guidelines 

SGLT2 inhibitors haven’t been available for long, but EndocrinologyNetwork.com has covered the basics in our SGLT2 topic center. See how you fare on our 6-question Basic Training Quiz. Links at the end will take you to articles on the pros, the cons, and more on this new class of antidiabetes drugs.

1. Which of the following is NOT a primary advantage of treatment with SGLT2 inhibitors?

C. Improved glycemia, A1c reductions (0.6% - 1%)

Answer: A. Neutral impact on hypoglycemia

2. SGLT2 inhibitors block the SGLT2 protein involved in what percentage of glucose reabsorption in the proximal renal tubule?

3. SGLT2 inhibitors are associated with a reduction in blood pressure of approximately:

4. As a result of their glucose-independent mechanism of action, SGLT2 inhibitors do not depend on level of Î²-cell function and are effective at all stages of disease

5. The FDA requires manufacturers of SGLT2 inhibitors to conduct post-marketing studies and pharmacovigilance programs to learn more about:

D. Pediatric safety/efficacy (bone health/development)

6. In patients with an estimated glomerular filtration rate (eGFR) of between 45 and 60 mL/min/1.73m

A. There is no dosage adjustment required for the 3 FDA-approved SGLT2 inhibitors at the 2 dosage strengths available for each

B. Canagliflozin and empagliflozin may only be dosed at the lower of the 2 strengths for each (100 mg and 10 mg, respectively)

C. Dapagliflozin is not recommended in patients with an eGFR <60 mL/min/1.73m

D. Empagliflozin not recommended in patients with an eGFR <60 mL/min/1.73m

Click here for answer and links to additional information.

Answer: A. There is no dosage adjustment required for the 3 FDA-approved SGLT2 inhibitors at the 2 dosage strengths available for each


The following articles from the EndocrinologyNetwork SGLT2 Topic Center provide more detailed information on all of the quiz questions and answers:

SGLT2 Inhibitors: Mechanism of Action, Pros, and Cons

SGLT2 Inhibitors: Pros, Cons, Comparisons, and Considerations

SGLT2 Inhibitors: 5 Things You Should Know

SGLT2 Inhibitors: 4 Points on Efficacy, Safety You Need to Know

Thank you for testing your SGLT2 knowledge. Please leave us a comment on the quiz, other material you would like to see included on EndocrinologyNetwork.com, or any thing else. -The Editors

The sodium glucose cotransporter-2 inhibitors are the newest diabetes drugs available. Have you got the basic concepts under your belt? Try these 6 questions and find out. 