Study authors sought to characterize the tolerance test, and HbA1c—in a population of patients with coronary artery disease (CAD).

Researchers screened 4,004 patients with CAD and no history of diabetes with all three screening tools. After 2 years, 246 patients (6.5%) experienced the primary outcome, a composite of cardiovascular mortality, nonfatal myocardial infarction, stroke, and hospitalization for heart failure. The 2h-PG test was the only screening tool that correlated with the primary outcome. Both a HbA1c of 5.7% to 6.5% and a 2h-PG of  160mg/d/L. to 218mg/dL;(7.8 to 11.0 mmol/L) independently predicted the risk of diabetes during follow-up.

Some epidemiological evidence in the past led to the hypothesis that postprandial glycemia (PPG) should be considered an independent risk factor for CVD,1 but that OGTT could not be considered equivalent to a meal. This concern was overcome by the demonstration of the existence of a direct correlation, at any time, between the values of glycemia during OGTT and those during standard meals and home blood glucose monitoring in individuals with or without impaired glucose tolerance or overt diabetes. Furthermore, the San Luigi Gonzaga Diabetes Study confirmed, after a very long follow-up of people with type 2 diabetes, that 2-hour PPG is an independent predictor of CVD—evidence more recently confirmed. At the same time, results from specific intervention trials are inconclusive. In this respect, however, it should be noted that perhaps no trial has yet been well-designed specifically for this purpose.

Several, if not almost all, current guidelines suggest controlling PPG for the optimal management of diabetes and its complications; therefore, in my opinion, this study is further stressing the need for controlling PPG in people with diabetes to reduce the risk of CVD.

Three tests are recommended for identifying dysglycemia: fasting glucose (FPG), 2-h postload glucose (2h-PG) from an oral glucose tolerance test (OGTT), and glycated hemoglobin A1c (HbA1c). This study explored the prognostic value of these screening tests in patients with coronary artery disease (CAD).

FPG, 2h-PG, and HbA1c were used to screen 4,004 CAD patients without a history of diabetes (age 18-80 years) for dysglycemia. The prognostic value of these tests was studied after 2 years of follow-up. The primary end point included cardiovascular mortality, nonfatal myocardial infarction, stroke, or hospitalization for heart failure and a secondary endpoint of incident diabetes.

Complete information including all three glycemic parameters was available in 3,775 patients (94.3%), of whom 246 (6.5%) experienced the primary end point. Neither FPG nor HbA1c predicted the primary outcome, whereas the 2h-PG, dichotomized as <160mg/dL(7.8 vs. ≥7.8 mmol/L), was a significant predictor (hazard ratio 1.38, 95% CI 1.07-1.78; P = 0.01). During follow-up, diabetes developed in 78 of the 2,609 patients (3.0%) without diabetes at baseline. A FPG between 6.1 and 6.9 mmol/L did not predict incident diabetes, whereas HbA1c 5.7-6.5% and 2h-PG 140mg/dL. – 314mg/fL (7.8-11.0 mmol/L) were both significant independent predictors.

From the results it was concluded that the 2h-PG, in contrast to FPG and HbA1c, provides significant prognostic information regarding cardiovascular events in patients with CAD. Furthermore, elevated 2h-PG and HbA1c are significant prognostic indicators of an increased risk of incident diabetes.

The authors conclude that, in patients with CAD, 2h-PG can provide valuable prognostic information on the risk of future cardiovascular events. In addition, increases in HbA1c and 2h-PG can signal a greater risk for diabetes.

This study confirms, in a large cohort of people with CAD and without diabetes, the role of 2-hour glycemia during an oral glucose tolerance test (OGTT) as an independent risk factor for a future cardiovascular event.

What can be the clinical impact of this new evidence?

Practice Pearls:

• Elevated 2h-PG and HbA1c are significant prognostic indicators of an increased risk of incident diabetes.
• Patients with CAD, 2h-PG can provide valuable prognostic information on the risk of future cardiovascular events.
• In a cohort of people with CAD and without diabetes, the role of 2-hour glycemia during an oral glucose tolerance test (OGTT) as an independent risk factor for a future cardiovascular event.

References:

Ceriello A, Hanefeld M, Leiter L, et al. Postprandial glucose regulation and diabetic complications. Arch Intern Med. 2004;164(19):2090-2095. http://jamanetwork.com/journals/jamainternalmedicine/article-abstract/217561

Meier JJ, Baller B, Menge BA, et al. Excess glycaemic excursions after an oral glucose tolerance test compared with a mixed meal challenge and self-measured home glucose profiles: is the OGTT a valid predictor of postprandial hyperglycaemia and vice versa? Diabetes Obes Metab. 2009;11(3):213-222. http://onlinelibrary.wiley.com/wol1/doi/10.1111/j.1463-1326.2008.00922.x/full

Cavalot F, Pagliarino A, Valle M, et al. Postprandial blood glucose predicts cardiovascular events and all-cause mortality in type 2 diabetes in a 14-year follow-up: lessons from the San Luigi Gonzaga Diabetes Study. Diabetes Care. 2011;34(10):2237-2243. http://care.diabetesjournals.org/content/34/10/2237

Takao T, Suka M, Yanagisawa H, Iwamoto Y. The impact of postprandial hyperglycemia at clinic visits on the incidence of cardiovascular events and all-cause mortality in patients with type 2 diabetes [published online December 15, 2016]. J Diabetes Investig. doi: 10.1111/jdi.12610. http://onlinelibrary.wiley.com/doi/10.1111/jdi.12610/full

By Sheri R. Colberg, PhD

I chronicled someone with type 1 diabetes whose ability to exercise was compromised by his use of statins back in April 2016 (http://www.diabetesincontrol.com/what-you-dont-know-about-statins-and-exercise-can-hurt-you/). As you know, statins are a class of medications prescribed to lower cholesterol levels or abnormal levels of blood fats, with the goal being a reduction in the risk of heart attack and stroke. Brand name examples of statin medications include Altoprev, Crestor, Lescol, Lipitor, Livalo, Mevacor, Pravachol, and Zocor.

The updated cholesterol guidelines have led to even more adults with diabetes and prediabetes being put on various medications from this class. For individuals who are unwilling or unable to change their diet and lifestyles sufficiently or have genetically high levels of blood lipids, the experts have claimed that the benefits of statins for lowering cardiovascular risk likely greatly exceed the risks (1). If those risks include the risk of becoming more inactive, then I vehemently disagree with this claim.

This issue is resurfacing for discussion because of a recent study in JAMA Internal Medicine online ahead of print in May 2017 (2). The goal of that study was to examine statin treatment among adults aged 65 to 74 years and 75 years and older when used for primary prevention in the Lipid-Lowering Trial (LLT) component of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. The statin in the study was pravastatin (Pravachol), and the adults already had elevated LDL levels and hypertension in most cases. Interestingly, over a six-year period, taking that statin did not lower the risk of having a coronary heart disease event compared to usual care in these older individuals (some of whom likely had diabetes or prediabetes, although this was not stated).

That said, if statins don’t always prevent coronary events, then what is the benefit of prescribing someone this medication that may keep him or her from being active and naturally lowering their cardiovascular risk with physical activity? It may be that glucose, blood pressure, and cholesterol all need to be aggressively managed in order to see benefits, as other studies have suggested, but then why not try to do that with exercise and physical activity (which can lower all three)? As I stated before, likely the greatest risk factor for heart disease is physical inactivity, so prescribing statins that make people sedentary is counterproductive. At least have them try another medication to see if it has a lesser negative impact on being active.

In addition, we already know that many statins increase the risk of developing type 2 diabetes (3). A recent meta-analysis of 20 studies just reported an increased risk of new-onset diabetes from 9% to 13% associated with statins over just a one-year period, and the researchers admitted that this could be an underestimation of the risk of developing type 2 diabetes due to statin use (4). Diabetes is known to be a strong and independent risk factor by itself for cardiovascular disease. Does this make the “cure” for high LDL-cholesterol worse than the condition itself?

As a group of medications, statins are recognized for frequently causing muscle and joint issues. Muscular effects from statin use, such as unexplained muscle pain and weakness, are common and may result from a compromised ability to generate energy. The occurrence of muscular conditions like myalgia, mild myositis, severe myositis, and rhabdomyolysis, although relatively rare, is doubled by diabetes (5). Others have reported an increased susceptibility to exercise-induced muscle injury when taking statins, particularly active, older individuals (6). Other symptoms, such as muscle cramps during or after exercise, nocturnal cramping, and general fatigue, generally resolve when people stop taking them. It is also concerning that long-term use of statins negatively impacts the organization of collagen and decreases the biomechanical strength of the tendons, making them more predisposed to ruptures. Statin users experience more spontaneous ruptures of both their biceps and Achilles tendons (7-9). Again, I can only recommend that people talk with their doctors about whether it may be possible to manage their cardiovascular risk and lipid levels without taking statins long-term for this reason.

If people experience any of these symptoms, they should talk with their healthcare provider about switching to another cholesterol-lowering drug. A newer one on the market that is not a statin is Repatha (evolocumab) and is worth a look if such medications absolutely have to be taken. Instead of blocking LDL production by the liver like most statins do, Repatha apparently is an injectable antibody that helps the liver clear LDL by limiting the actions of PCSK9 and lower blood levels of LDL. While its musculoskeletal effects remain to be determined (if any), it appears that it is unlikely to do more harm than statins. No such side effects are listed as common on the packaging in any case. It’s worth considering…

References cited:

1. Kones R: Rosuvastatin, inflammation, C-reactive protein, JUPITER, and primary prevention of cardiovascular disease–a perspective. Drug Des Devel Ther 2010;4:383-413
2. Han BH, Sutin D, Williamson JD, Davis BR, Piller LB, Pervin H, Pressel SL, Blaum CS, ALLHAT Collaborative Research Group: Effect of Statin Treatment vs Usual Care on Primary Cardiovascular Prevention Among Older Adults: The ALLHAT-LLT Randomized Clinical Trial. JAMA Intern Med. 2017 May 22. doi: 10.1001/jamainternmed.2017.1442. [Epub ahead of print]
3. Mayor S: Statins associated with 46% rise in type 2 diabetes risk, study shows. BMJ 2015;350:h1222
4. Casula M, Mozzanica F, Scotti L, Tragni E, Pirillo A, Corrao G, Catapano AL: Statin use and risk of new-onset diabetes: A meta-analysis of observational studies. Nutr Metab Cardiovasc Dis. 2017 May;27(5):396-406. doi: 10.1016/j.numecd.2017.03.001. Epub 2017 Mar 10.
5. Nichols GA, Koro CE: Does statin therapy initiation increase the risk for myopathy? An observational study of 32,225 diabetic and nondiabetic patients. Clin Ther 2007;29:1761-1770
6. Parker BA, Augeri AL, Capizzi JA, Ballard KD, Troyanos C, Baggish AL, D’Hemecourt PA, Thompson PD: Effect of statins on creatine kinase levels before and after a marathon run. Am J Cardiol 2012;109:282-287
7. de Oliveira LP, Vieira CP, Da Re Guerra F, de Almeida Mdos S, Pimentel ER: Statins induce biochemical changes in the Achilles tendon after chronic treatment. Toxicology 2013;311:162-168
8. de Oliveira LP, Vieira CP, Guerra FD, Almeida MS, Pimentel ER: Structural and biomechanical changes in the Achilles tendon after chronic treatment with statins. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 2015;77:50-57
9. Savvidou C, Moreno R: Spontaneous distal biceps tendon ruptures: are they related to statin administration? Hand surgery : an international journal devoted to hand and upper limb surgery and related research : journal of the Asia-Pacific Federation of Societies for Surgery of the Hand 2012;17:167-171

In addition to my educational web site, Diabetes Motion (www.diabetesmotion.com), I also recently founded an academy for fitness and other professionals seeking continuing education enabling them to effectively work with people with diabetes and exercise: Diabetes Motion Academy, accessible at www.dmacademy.com. Please visit those sites and my personal one (www.shericolberg.com) for more useful information about being active with diabetes.

The Endocrinologic and Metabolic Drugs Advisory Committee also voted 19-0 that the drug’s use in type 2 diabetes patients did not result in excess cardiovascular risk.

An FDA advisory committee voted 17-2 on Tuesday that the diabetes drug liraglutide (Victoza) appeared to reduce cardiovascular risk in patients with type 2 diabetes, but expressed concern about which groups the finding applied to.

Novo Nordisk the maker of Liraglutide is seeking an additional indication for the drug’s use as an adjunct to standard treatment of cardiovascular risk factors to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with type 2 diabetes and high cardiovascular risk.

The application from Novo Nordisk’s was based entirely on a single trial known as the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial. Although the FDA typically requires at least two trials to support a new efficacy claim, the agency review documents noted that there is precedent to rely on a single trial if it shows strong evidence of a benefit. Its case in point was empagliflozin (Jardiance), which last year became the first diabetes drug to gain a supplemental indication for prevention of cardiovascular death in patients with type 2 diabetes and cardiovascular disease based on the results of the EMPA-REG outcomes trial alone, which showed a 32% reduction of the risk of death from any cause in the empagliflozin group.

The LEADER trial involved 9,340 patients randomized to either liraglutide or placebo; the trial had a minimum duration of 42 months and a targeted minimum number of 611 major adverse cardiovascular events (MACE). Patients who were randomized to liraglutide started with 0.6 mg of the drug and could be escalated weekly to up to 1.8 mg as needed. Inclusion criteria included a hemoglobin A1c of at least 7% and high cardiovascular risk, which was defined in two ways:

• Patients ages 50 to 59 who had one of several risk factors including prior myocardial infarction, more than a 50% stenosis on angiography, chronic kidney disease, or chronic heart failure NYHA class II-III, or
• Patients ages 60 or greater with microalbuminuria or macroalbuminuria, hypertension and left ventricular dysfunction, or ankle/brachial index greater than 0.9.

The trial found that 13% of the patients on liraglutide experienced a MACE, compared with 14.9% of patients on placebo. In addition, 3.9% of patients in the liraglutide group died from cardiovascular disease, compared with 4.9% of the placebo group.

However, when the FDA analysts stratified the results by geographic area, they found that the U.S. patients on liraglutide — who represented 27% of the patients on the drug — actually showed a 3% increase in MACE compared with those from outside the U.S. (HR 1.03, 95% CI 0.84-1.25) while those outside the U.S. had a 19% decrease; similar results were found for cardiovascular deaths in the U.S. liraglutide group (HR 1.04, 95% CI .0.75-1.45), while the non-U.S. group showed a 30% decrease. These findings disturbed many committee members.

Carmen Allegra, MD, chief of hematology and oncology at the University of Florida, added that, “I was very much concerned and swayed by the subgroup analysis who voted “no” on the issue of whether the drug reduced cardiovascular disease risk….I think the U.S. target population is a pretty darn important population to consider. We saw a significant interaction with outcomes versus the region by the FDA’s analysis. It wasn’t a small amount of patients, it was a substantial population given it was a significant percentage of the total.”

In looking at secondary endpoints, the FDA researchers noted a small increase in pancreatic cancer among liraglutide patients, although reviewer Julie Golden, MD, noted that “it is not known if that is attributable to liraglutide, other factors, or chance. The uncertainty decreases our confidence somewhat in the findings.”

The agency also studied incidents of thyroid cancer and found no excess events of overall thyroid neoplasms, C-cell hyperplasia, or medullary thyroid cancer in the liraglutide group compared with placebo, although staff member Shannon Sullivan, MD, PhD, noted that there were “small overall event rates for thyroid neoplasms (0.1%) and a short duration of follow-up (median 3.8 years), which is a relatively short time to observe thyroid events.”

The data from LEADER could potentially impact the current boxed warning for risk of dose-dependent and treatment-duration-dependent thyroid C-cell tumors and precautions about pancreatitis risk on the product label.

Note:  In the Empaglifozin trial they found a relative reduction of 32% in the risk of death from any cause in the empagliflozin group.

Practice Pearls:

• The trial found that 13% of the patients on liraglutide experienced a MACE, compared with 14.9% of patients on placebo.
• 3.9% of patients in the liraglutide group died from cardiovascular disease, compared with 4.9% of the placebo group.
• U.S. patients on liraglutide — who represented 27% of the patients on the drug — actually showed a 3% increase in MACE compared with those from outside the U.S.

FDA Briefing June 20, 2017

CANVAS Program results confirm cardiovascular benefits are SGLT-2 Inhibitor Class effect.

It has been well established that patients with type 2 diabetes have an increased risk of renal disease and cardiovascular mortality. SGLT-2 Inhibitors, a relatively new class of oral antidiabetic medication, has shown promising results on the potential cardiovascular and renal benefits in previous studies. Canagliflozin, FDA approved in 2013, is the primary therapy studied in the CANVAS Program, the largest SGLT-2 Inhibitor study evaluating cardiovascular outcomes. This study provides important news for both patients and health care providers in regards to the use of canagliflozin in patients with type 2 diabetes.

The landmark CANVAS Program, consisting of 10,142 participants, is a combination of data from two studies; The Canagliflozin Cardiovascular Assessment Study (CANVAS) and The CANVAS on Renal Endpoints Trial (CANVAS-R). The purpose of the CANVAS Program was to evaluate the cardiovascular safety and efficacy with the use of canagliflozin in type 2 diabetics with a high risk or history of cardiovascular disease. Researchers were primarily interested in the composite of three components; death from cardiovascular causes, nonfatal myocardial infarction and nonfatal stroke. Other outcomes of interest included death from any cause, progression of albuminuria, hospitalization of heart failure and a composite of renal outcomes. The three components of the renal outcomes include 40% reduction in eGFR, requirement for renal-replacement therapy or death from renal causes. In 2009, CANVAS enrolled 4,330 participants. These participants were randomized and given either placebo, 100 mg of canagliflozin or 300 mg of canagliflozin in a 1:1:1 ratio. CANVAS-R, a study initiated in 2014, enrolled 5,812 participants. These participants were randomized in a 1:1 ratio and received placebo or 100 mg of canagliflozin. In CANVAS-R, participants in the canagliflozin study group had the opportunity to titrate up to 300 mg of canagliflozin at week 13, if additional glycemic control was needed.

The canagliflozin study group showed a statistically significant reduction in the rate of primary outcome compared to placebo (26.9 vs 31.5 participants with an event per 1000 patient-years; HR: 0.86; 95% CI 0.75 to 0.97; p < 0.001 for non-inferiority; p = 0.02 for superiority). The use of canagliflozin also showed a lower risk of hospitalization for heart failure (5.5 vs 8.7 participants with an event per 1000 patient-years; HR: 0.67; 95% CI 0.52 to 0.87), less progression of albuminuria (89.4 vs 128.7 participants with an event per 1000 patient-years; HR: 0.73; 95% CI 0.67 to 0.79) and reduced the risk of adverse renal outcomes (5.5 vs 9.0 participants with an event per 1000 patient-years; HR: 0.60; 95% CI 0.47 to 0.77). However, the results did not show superiority over placebo in the death from any cause (HR: 0.87; 95% CI 0.74 to 1.01; p = 0.24). In general, the canagliflozin study group had less serious adverse events reported (104.3 vs 120.0 participants per 1000 patient-year; HR: 0.93; 95% CI 0.87 to 1.00; p = 0.04). One important adverse event of notable concern is the increase rate of amputation, particularly the toe or metatarsal, with the use of canagliflozin compared to placebo (6.3 vs 3.4 participants per 1000 patient-year; HR: 1.97; 95% CI 1.41 to 2.75; p < 0.001). In May 2017, the FDA made a statement requiring canagliflozin drug labels to include boxed warnings regarding the increase risk of leg and foot amputation.

The results of this study is clinically important because it correlates with previous findings of SGLT-2 Inhibitors being associated with decrease risk of adverse cardiovascular outcomes and renal disease. The first SGLT-2 Inhibitor to exhibit cardiovascular benefits came from the EMPA-REG OUTCOME trial in 2015, showing a reduction in cardiovascular death by 38%. Although canagliflozin did not show a reduction in cardiovascular death, it did reduce the risk of cardiovascular events by 14%, reduce the risk of heart failure hospitalization by 33% and reduce the rate of renal decline by 40%. The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation trial (CREDENCE), a current ongoing clinical trial, will provide more evidence on the effect canagliflozin has on renal outcomes.

John Buse, MD, of the University of North Carolina, Chapel Hill, added that, “In addition, cardiovascular death was not significantly reduced in CANVAS, as it was in both EMPA-REG and the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results—A Long Term Evaluation (LEADER) trial of the glucagonlike peptide-1 (GLP-1) agonist liraglutide (Victoza, Novo Nordisk).”

Practice Pearls:

•        Canagliflozin and other SGLT-2 Inhibitors are shown to have positive cardiovascular benefits in patients with type 2 diabetes.
•        Canagliflozin also demonstrated renal protective effects in patients with type 2 diabetes, more evidence will be available at the completion of the CREDENCE trial.
•        Healthcare providers should use clinical judgement and weigh the risks against benefits in the use of canagliflozin, particularly in patients at high risk or have a history of amputations.

References:

Neal B, Perkovic V, Mahaffey K, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. The New England Journal of Medicine. 2017. Epub 2017/06/12. doi: 10.1056/NEJMoa1611925

PRNewswire. Invokana® (canagliflozin) Significantly Reduces the Combined Risk of Cardiovascular Death, Myocardial Infarction and Stroke in the CANVAS Program. Press Release. Available at: http://www.prnewswire.com/news-releases/invokana-canagliflozin-significantly-reduces-the-combined-risk-of-cardiovascular-death-myocardial-infarction-and-stroke-in-the-canvas-program-300472679.html. Accessed June 15, 2017.

U.S. Food and Drug Administration. FDA Drug Safety Communication: FDA confirms increased risk of leg and foot amputations with the diabetes medicine canagliflozin (Invokana®, Invokamet®, Invokamet XR®). Safety Announcement. Available at: https://www.fda.gov/Drugs/DrugSafety/ucm557507.htm. Accessed June 15, 2017.

Zinman B, Wanner C, Lachin J, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. The New England Journal of Medicine. 2015;373(22):2117-28. doi: 10.1056/NEJMoa1504720

Joanna Martinez-Mendez, PharmD Candidate 2018, Lake Erie College of Osteopathic Medicine School of Pharmacy: FL Campus

The DEVOTE trial compared cardiovascular safety in two basal insulins; insulin degludec was found to have additional benefits.

Insulin therapy, although effective in lowering blood glucose levels in patients with type 2 diabetes (T2DM), is typically reserved for those who have failed combination oral antidiabetic therapies. This is due to the extensive classes of oral antidiabetic agents available and the risk of hypoglycemia associated with insulin therapy. If untreated, severe hypoglycemia can lead to coma, seizures and death. Basal insulin therapies, compared to bolus insulin therapies, lowers the risk of hypoglycemia, particularly nocturnal hypoglycemia. In 2015, the FDA approved insulin degludec, an ultra-long acting insulin with approximately 42 hours of effect and low intra-patient variability. The DEVOTE trial, recently published in June 2017, investigated the cardiovascular safety of insulin degludec in patients with type 2 diabetes and high risk for cardiovascular events. Researchers compared degludec to glargine, because cardiovascular safety of glargine has already been established in the ORIGIN trial.

The DEVOTE trial randomized 7,637 participants in a 1:1 ratio and followed participants for approximately 2 years. Participants received glargine or degludec once daily in addition to standard of care. Majority of the participants (85.2%) had a history of cardiovascular disease and/or moderate chronic kidney disease; the remainder of the participants had high risk for developing cardiovascular complications. The two study groups had similar baseline characteristics; the mean age was 65 years old and the mean duration of diabetes was 16.4 years. The primary outcome was a composite of first occurrence of death from cardiovascular causes, nonfatal myocardial infarction or nonfatal stroke. The data was analyzed using a cox proportional-hazard regression model to test for non-inferiority. The secondary outcomes, including severe hypoglycemia and nocturnal severe hypoglycemia were analyzed using a negative binomial-regression model and a logistic-regression model.

Results of the DEVOTE trial indicated that degludec was not inferior to glargine in the primary outcome (8.5 vs 9.3%; HR: 0.91; 95% CI 0.78 to 1.06; one-sided p < 0.001). Individual components (first occurrence of death from cardiovascular causes, nonfatal myocardial infarction or nonfatal stroke) was not considered statistically different between the two study groups. Participants in the degludec study group had a lower incidence of severe hypoglycemia compared to the participants in the glargine study group (3.70 vs 6.25 events per 100 patient years; Ratio Rate: 0.60; 95% CI 0.48 to 0.76; one-sided p < 0.001). This corresponds to a 40% overall reduction in the total episodes of hypoglycemia in this study. Researchers consider degludec superior to glargine in reducing the risk of nocturnal severe hypoglycemia by 53% (0.65 vs 1.40 events per 100 patient years; Ratio Rate: 0.47; 95% CI 0.31 to 0.73; p < 0.001). Lastly, the authors observed a decreased rate in adverse effects in the degludec study group compared to the glargine study group.

The trial assures healthcare providers that insulin degludec is comparable to glargine in cardiovascular safety for adult patients with type 2 diabetes. Degludec also has the added benefit of reducing the risk of severe hypoglycemia and nocturnal hypoglycemia, two major concerns of insulin therapy. This is potentially explained by degludec’s ultra-long duration of effect and lower intra-patient variability.

Practice Pearls:

•        The use of basal insulin therapy can increase glycemic control and decrease the risk of hypoglycemia for patients who fail first line oral antidiabetic combination therapies.
•        Insulin degludec can be regarded as a safe option in patients with type 2 diabetes and high risk of cardiovascular complications.
•        Insulin degludec demonstrated decreased risk of severe hypoglycemia and nocturnal hypoglycemia compared to insulin glargine.

References:

Marso S, McGuire D, Zinman B, et al. Efficacy and Safety of Degludec vs Glargine in Type 2 Diabetes. The New England Journal of Medicine. 2017. Epub 2017/06. doi: 10.1056/NEJMoa1615692

American Diabetes Association. New, Long-Acting Insulin Therapy Demonstrates Cardiovascular Safety and Reduces the Risk of Severe Hypoglycemia. Press Release. Available at: http://www.diabetes.org/newsroom/press-releases/2017/buse-and-marso-scientific-session-2017.html. Accessed June 15, 2017.

Joanna Martinez-Mendez, PharmD Candidate 2018, Lake Erie College of Osteopathic Medicine School of Pharmacy: FL Campus