American College of Physicians: Internal Medicine — Doctors for Adults ®

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ACP DiabetesMonthly



In the News for the month of May 2013




Highlights

Half of diabetics do not meet recommended care goals

Almost half of U.S. adults with diabetes did not meet recommended goals for diabetes care, despite improvements in controlling risk factors and adhering to preventive practices from 1999 to 2010, a study concluded. More...

New calculator predicts two-year mortality risk in type 2 diabetes

Researchers have developed a new Web-based calculator that predicts short-term mortality risk in patients with type 2 diabetes. More...

Aspirin therapy not associated with cardiovascular benefit in type 2 diabetes

Aspirin showed no cardiovascular benefit and may have been associated with worse outcomes in a recent study of patients with type 2 diabetes. More...


Test yourself

MKSAP Quiz: hypoglycemia unawareness

This month's quiz asks readers to evaluate a 33-year-old woman with multiple recent episodes of severe hypoglycemia. More...


From ACP InternistWeekly

Mortality, hospitalization may be similar with sitagliptin versus other oral antidiabetics

Sitagliptin was associated with similar rates of hospital admission and mortality as other glucose-lowering drugs, according to a recent study of patients with type 2 diabetes. More...

Consensus statement offers strategies for preventing hypoglycemia

Consequences of hypoglycemia and strategies to prevent this condition in patients with diabetes were discussed in a recent consensus statement from the American Diabetes Association (ADA) and The Endocrine Society. More...

Metformin appears safe for heart failure patients, analysis finds

Metformin appears to be a safe option for glycemic control in heart failure patients, according to a recent meta-analysis. More...


From ACP Internist

Patients with diabetes facing vision loss at ever-earlier ages

The growing problem of diabetic retinopathy in young people and the need for response by primary care clinicians are discussed in the April ACP Internist. More...


From ACP Journal Club

Review: Dipeptidyl peptidase-4 inhibitors do not increase overall adverse events in type 2 diabetes

A meta-analysis included 67 randomized controlled trials comparing dipeptidyl peptidase-4 (DPP-4) inhibitors to placebo or other oral antidiabetic agents. More...

Metformin reduced CV events compared with glipizide in patients with type 2 diabetes and CAD

A multicenter randomized controlled trial of Chinese patients with type 2 diabetes and coronary artery disease found that metformin reduced cardiovascular events more than glipizide at 5 years. More...


Tool of the month

What do I need to tell my patients about hypoglycemia?

Some key messages should be given to patients about avoiding and treating hypoglycemia. More...


FDA update

Single and combo diabetes drugs approved

Alogliptin (Nesina) and two new combination drugs (alogliptin and metformin hydrochloride [Kazano] and alogliptin and pioglitazone [Oseni]) were approved by the FDA to improve blood glucose control in adults with type 2 diabetes, along with diet and exercise. More...

Incretin mimetics' effects on pancreas under investigation

The FDA is investigating reports of possible increased risk of pancreatitis and precancerous findings of the pancreas from incretin mimetic drugs for type 2 diabetes. More...


Keeping tabs

Spotlight on bariatric surgery

Treatment of type 2 diabetes with bariatric surgery was discussed by several recent publications, including updated guidelines from a group of medical specialty organizations. More...


Physician editor: David V. O'Dell, MD, FACP



Highlights


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Half of diabetics do not meet recommended care goals

Almost half of U.S. adults with diabetes did not meet recommended goals for diabetes care, despite improvements in controlling risk factors and adhering to preventive practices from 1999 to 2010, a study concluded.

Researchers analyzed data for adults with self-reported diabetes: 3,355 people from the National Health and Nutrition Examination Survey and 97,310 from the Behavioral Risk Factor Surveillance System, from the years 1999 to 2010. Results were published by the New England Journal of Medicine on April 25.

Between the 1999-to-2002 period and the 2007-to-2010 period, the proportion of patients with a hemoglobin A1c (HbA1c) level over 9% decreased by 5.8 percentage points (95% CI, −10.5 to −1.1), while the proportion with an HbA1c under 7% increased by 7.9 percentage points (95% CI, 0.8 to 15.0). The proportion with blood pressure under 130/80 mm Hg increased by 11.7 percentage points (95% CI, 5.7 to 17.7). The proportion with LDL cholesterol level under 100 mg/dL increased by 20.8 percentage points (95% CI, 11.6 to 30.0). Still, by the later time period, only 14.3% of surveyed diabetics did not smoke and met all three targets for glycated hemoglobin, blood pressure control, and LDL cholesterol.

A comparison of data from 2000 and 2008 showed nonsignificant drops in the number of people receiving annual eye examinations and dental exams. However, more people received annual checks of lipid levels, annual foot examinations, annual influenza vaccinations, pneumococcal vaccination, at least daily self-monitoring of glucose, diabetes education at diagnosis, or angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers.

In 2007-2010, more than 73.4% of participants underwent annual eye examinations, 71.4% underwent foot examinations, 88.2% underwent lipid checks and 70.9% performed self-monitoring of glucose levels. Also, 49% to 60% reported receiving vaccinations and 54.6% reported receiving diabetes education. However, only 22.4% of diabetics underwent annual influenza vaccination, and had both eye and foot examinations in 2008.

The researchers wrote, "We noted that younger adults were less likely than older adults to meet goals for treatment and preventive practices; furthermore, younger adults had no significant improvements in these areas over time. It is unclear whether physician inattentiveness, poor access to health care, or other factors account for these gaps. Because early control of the risk factors for microvascular and macrovascular disease may confer benefits, these results suggest that younger adults with diabetes need further attention."


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New calculator predicts two-year mortality risk in type 2 diabetes

Researchers have developed a new Web-based calculator that predicts short-term mortality risk in patients with type 2 diabetes.

The researchers investigated two cohorts of patients. The first "training set" comprised 679 white Italian patients with type 2 diabetes who were followed for more than seven years. The second "validation set" comprised 936 white Italian patients with diabetes who were followed for approximately 4.5 years. In both cases, the only exclusion criterion was poor life expectancy due to malignancy. Both sets were tracked for all-cause mortality via check-ins with city registry offices, or phone calls to the patient or relatives. Results were published online May 1 in Diabetes Care.

Nine variables were significantly associated with two-year all-cause mortality and were used to make a final predictive model (C statistic, 0.88 in training set and 0.82 in validation set). Those variables were age, body mass index, diastolic blood pressure, LDL cholesterol, triglycerides, HDL cholesterol, urine albumin-to-creatinine ratio, antihypertensive therapy, and insulin therapy. Researchers then used an algorithm to identify patients at intermediate and high risk of death (hazard ratios, 7.0 and 24.4, respectively, compared with those at low risk) and developed a Web-based risk calculator (available at www.operapadrepio.it/rcalc/rcalc.php).

This is the first known study to develop a well-performing model for predicting death in type 2 diabetes that was then validated in a second independent sample, the authors wrote. Study limitations include lack of information on causes of death and on previous cardiovascular events (a major risk factor for all-cause death) and unknown generalizability to non-Italian patients, they wrote. Still, the initial results seem promising and may help clinicians prioritize resources "for targeting aggressive preventive and treatment strategies in a subset of very high-risk individuals," the authors concluded.


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Aspirin therapy not associated with cardiovascular benefit in type 2 diabetes

Aspirin showed no cardiovascular benefit and may have been associated with worse outcomes in a recent study of patients with type 2 diabetes.

Researchers in Sweden performed a population-based cohort study in hospital outpatient clinics and primary care practices to determine the risks and benefits of aspirin therapy in patients who had type 2 diabetes but no previous cardiovascular disease (CVD) at baseline. The study period covered 2005 to 2009, with a mean follow-up of 3.9 years. All included patients were registered in the Swedish National Diabetes Register and received continuous low-dose aspirin treatment or no aspirin treatment. The main outcome measures were risk for CVD, coronary heart disease (CHD), stroke, death and bleeding in patients taking aspirin compared with no aspirin. The study was published on April 20 by BMJ Open.

The aspirin group included 4,608 patients, while the no-aspirin group included 14,038 patients. Approximately 55% of patients in each group were men. Patients ranged in age from 30 to 80 years. The authors found no association between aspirin use and any positive effects on patients' risk for CVD or death but did find an association with increased risk for both nonfatal and fatal CHD (hazard ratio, 1.19; 95% CI, 1.01 to 1.41; P=0.04). When analyzed separately by gender, women taking aspirin had an increased risk for CHD (hazard ratio, 1.41; 95% CI, 1.07 to 1.87; P=0.02) and CVD (hazard ratio, 1.28; 95% CI, 1.01 to 1.61; P=0.04), but the men taking aspirin did not. Aspirin was also associated with a trend toward increased risk for bleeding (hazard ratio, 1.41; 95% CI, 0.99 to 1.99).

The authors noted that residual confounding could not be ruled out and that some patients categorized as without CVD at baseline could in fact have had mild CVD that was not detected. However, they concluded that their results do not suggest any beneficial effects of aspirin in patients with type 2 diabetes but no preexisting CVD and "support the trend towards more restrictive use of aspirin" in this population. They also called for more research into the apparent differences between men and women in this area.



Test yourself


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MKSAP Quiz: hypoglycemia unawareness

A 33-year-old woman is evaluated after having three episodes of severe hypoglycemia, each resulting in a visit to the emergency department, in the past month. Two of the episodes occurred while she was asleep, and the most recent one happened midafternoon yesterday. The patient has a 19-year history of type 1 diabetes mellitus and has been trying to lower her hemoglobin A1c level to less than 7.0% before she tries to get pregnant. She states that she no longer experiences any warning symptoms before she becomes hypoglycemic. The patient had an episode of diabetic ketoacidosis in her teens. She has mild background diabetic retinopathy, some numbness in her feet from peripheral neuropathy, and occasional orthostatic hypotension. She eats a healthy diet, counts carbohydrates, and adjusts her preprandial insulin intake. Medications are insulin glargine, 24 units at bedtime, and insulin glulisine, 6 to 10 units before breakfast, lunch, and dinner, depending on her planned carbohydrate intake and preprandial blood glucose level.

On physical examinations, vital signs are normal; BMI is 30.

Results of laboratory studies show a hemoglobin A1c value of 6.6% and no evidence of microalbuminuria.

Which of the following is the most appropriate treatment for this patient?

A. Increased carbohydrate intake at meals
B. Insulin dose reductions
C. α-Lipoic acid
D. Preprandial pramlintide
E. Substitution of insulin detemir for insulin glargine

Click here or scroll to the bottom of the page for the answer and critique.


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From ACP InternistWeekly


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Mortality, hospitalization may be similar with sitagliptin versus other oral antidiabetics

Sitagliptin was associated with similar rates of hospital admission and mortality as other glucose-lowering drugs, according to a recent study of patients with type 2 diabetes.

The observational, retrospective study used a database of commercial insurance claims to find more than 72,000 U.S. patients who began taking an oral antidiabetic drug between 2004 and 2009. They were followed until death, termination of insurance or the end of 2010. The study's composite endpoint was all-cause hospital admission and all-cause mortality. Results were published by BMJ on April 25.

Of the 72,738 patients, 11% took sitagliptin; of those, 91% took it in combination with at least one other antidiabetic agent. In the total study population, 11% of patients had ischemic heart disease and 9% had diabetes complications when their first diabetes drug was prescribed. Sitagliptin users were slightly more likely to have diabetes complications and to use insulin at the start of treatment. Overall, 20% of the studied patients died or were admitted to the hospital, and sitagliptin users had a similar rate of this outcome compared with other patients (adjusted hazard ratio [HR] 0.98; 95% CI, 0.91 to 1.06), even if they had ischemic heart disease (HR, 1.10; 95% CI, 0.94 to 1.28) or estimated glomerular filtration rate below 60 mL/min (HR, 1.11; 95% CI, 0.88 to 1.41).

The results of this first population-based study of a dipeptidyl peptidase-4 (DPP-4) inhibitor's effect on mortality and hospitalization are consistent with previous observational studies showing that sitagliptin isn't associated with increased acute pancreatitis. However, the results don't confirm recent meta-analyses finding a major reduction in adverse cardiac events in patients on the drug, the study authors noted. That could be due to the higher baseline risk of patients taking sitagliptin in the current study. The study's observational nature and relatively short follow-up were two limitations.

Definitive conclusions about the safety of sitagliptin in patients with cardiovascular disease will only be possible after the conclusion of a large, currently ongoing trial, the study authors noted. Still, the results of this observational study support current recommendations for use of sitagliptin and indicate that the drug seems to be safe in patients with diabetes. "Given the current controversy about other antidiabetic agents, most notably the thiazolidinediones, this is important information for patients and for clinicians," the study authors wrote.


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Consensus statement offers strategies for preventing hypoglycemia

Consequences of hypoglycemia and strategies to prevent this condition in patients with diabetes were discussed in a recent consensus statement from the American Diabetes Association (ADA) and The Endocrine Society.

The statement updated a 2005 ADA workgroup report. Experts from both specialty organizations considered data from recent clinical trials and other studies and also used expert opinion to develop their conclusions. The statement was published in Diabetes Care and the Journal of Clinical Endocrinology and Metabolism on April 15.

The consensus statement confirmed previous definitions of hypoglycemia and noted several challenges of accurately measuring blood glucose (such as the inaccuracies of point-of-care meters in critical care settings). Although hypoglycemia occurs more frequently in patients with type 1 diabetes, the greater prevalence of type 2 diabetes means that most episodes occur in type 2 patients, the consensus authors noted. Recent evidence (including the ACCORD, ADVANCE and VADT trials) indicates that hypoglycemia may negatively affect mortality and cognitive function, especially in patients with type 2 disease.

Elderly patients are particularly vulnerable to hypoglycemia, the consensus statement noted. Therefore, for these patients, the experts recommended careful education and regular reinforcement regarding the symptoms and treatment of hypoglycemia, assessment of functional status to properly apply individualized goals, avoidance of arbitrary short-acting insulin sliding scales and glyburide, simplification of complex regimens, and education about hypoglycemia for caregivers and staff in long-term care facilities.

In general, glycemic targets should be based on a patient's age, life expectancy, comorbidities, preferences and an assessment of how hypoglycemia might impact his or her life, the statement said. For healthy adults with diabetes, a reasonable goal might be the lowest hemoglobin A1c level that does not cause severe hypoglycemia, preserves awareness of hypoglycemia and doesn't result in an unacceptable number of hypoglycemic episodes. For patients with long-standing disease and advanced complications or limited life expectancy, the goals may be relaxed.

Strategies to prevent hypoglycemia include patient education (for both the patient and any domestic companions, possibly including interviewing to help identify precipitating factors of hypoglycemic episodes), dietary interventions (such as carrying carbohydrates at all times), exercise management, medication adjustment (substitution of rapid-acting insulin for regular insulin or other oral agents for sulfonylureas), and glucose monitoring. Clinicians should also assess the risk of hypoglycemia at every visit with patients on insulin or insulin secretagogues (an example questionnaire is provided in the consensus statement) and carefully review the patient's glucose log for date, time and circumstances of any hypoglycemia episodes.


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Metformin appears safe for heart failure patients, analysis finds

Metformin appears to be a safe option for glycemic control in heart failure patients, according to a recent meta-analysis.

The analysis included nine observational studies of the association between metformin and morbidity and mortality in patients with diabetes and heart failure, the majority of which were published in 2010. According to the analysis, patients on metformin had about 20% lower mortality than controls, who were most commonly taking sulfonylurea drugs: 23% versus 37% (P<0.001). A small but not statistically significant reduction in all-cause hospitalizations was also found in the metformin patients compared to controls.

The researchers also looked at the subgroups of patients who had reduced left ventricular ejection fraction (LVEF) or chronic kidney disease, and in both cases, metformin was associated with slightly reduced mortality (pooled adjusted risk estimates, 0.91 and 0.81, respectively). No increased risk of lactic acidosis was found in metformin patients. The results were published online by Circulation Heart Failure on March 18.

Despite historical concerns about its use in heart failure patients, metformin appears to be at least as safe as other glucose-lowering treatments for these patients (including the high-risk groups with reduced LVEF and kidney disease) and should be the treatment of choice, the study authors concluded. This finding supports both current guidelines from medical specialty societies and recent decisions by the FDA and Canadian regulators to remove a black-box contraindication concerning use of metformin in heart failure patients.

The authors did acknowledge a risk of confounding because the evidence is based entirely on observational trials, but they said that randomized trials in this patient population are rare and not likely to be expanded. However, a number of studies in animal models of heart failure have suggested potential benefits of metformin, the authors noted.



From ACP Internist


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Patients with diabetes facing vision loss at ever-earlier ages

Just as diabetes is affecting younger populations, so are its consequences. Childhood obesity can translate into diabetic retinopathy in patients in their 20s.

Learn how the primary care community should respond in the April ACP Internist.



From ACP Journal Club


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Review: Dipeptidyl peptidase-4 inhibitors do not increase overall adverse events in type 2 diabetes

A meta-analysis included 67 randomized controlled trials (RCTs) comparing dipeptidyl peptidase-4 (DPP-4) inhibitors to placebo or other oral antidiabetic agents. The rates of adverse events, serious adverse events, and mortality were no higher in patients taking DPP-4 inhibitors than in the overall group. However, compared with placebo, DPP-4 inhibitors increased risk for hypoglycemia when insulin or a sulphonylurea was coadministered.

The study was published in Diabetes, Obesity and Metabolism in December 2012. The following commentary by Saurav Chatterjee, MD, and Sanjay Chatterjee, MD, was published in the ACP Journal Club section of the April 16 Annals of Internal Medicine.

The meta-analysis by Gooßen and Gräber has important implications for clinical medicine as it indicates that the gliptins, currently widely used in clinical practice, do not increase risk for such infections as nasopharyngitis, upper respiratory infections, or urinary tract infections. It thereby refutes prior publications that have indicated such a possibility.

The statistically significant findings for specific types of adverse effects may be robust considering the large sample size of the review and longer follow-up compared with previously reported meta-analyses. However, weaknesses are similar to previous meta-analyses of gliptins in not adjusting for multiple testing and not stringently defining and specifying the outcomes evaluated, including cardiac and vascular disorders, and hypoglycemia; therefore, findings of increased vascular and cardiac disorders in patients treated with gliptins need to be interpreted cautiously. However, these data do provide some evidence for continuing gliptins in patients with such minor infections as upper respiratory infections, urinary tract infections, and skin infections, while the pragmatic practitioner will probably switch to insulin in patients with more severe infections.

This review could be used as a basis for generating the hypotheses for adequately powered RCTs to rigorously and conclusively corroborate or refute the signals noted in this meta-analysis.


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Metformin reduced CV events compared with glipizide in patients with type 2 diabetes and CAD

A multicenter randomized controlled trial (RCT) of Chinese patients with type 2 diabetes and coronary artery disease (CAD) found that metformin reduced cardiovascular events more than glipizide at 5 years.

The study was published by Diabetes Care on Dec. 10, 2012. The following commentary by Michael Tanner, MD, FACP, was published in the ACP Journal Club section of the April 16 Annals of Internal Medicine.

In SPREAD-DIMCAD, Hong and colleagues randomized 304 high-risk Chinese patients with CAD and mild type 2 diabetes (mean hemoglobin A1c 7.6%) to metformin or glipizide plus placebo 3 times per day for 3 years, with insulin added as needed. The primary outcome was a composite of death, stroke, MI, or revascularization. Metformin and glipizide both reduced hemoglobin A1c (7.0% and 7.1%, respectively), yet the metformin group had fewer CV events (P=0.026).

In simple hypertension, it matters more that blood pressure is reduced than how it is reduced. The SPREAD-DIMCAD findings show that the opposite is true in diabetes: How matters. There is more to stroke and MI prevention than just glucose control.

The authors note that metformin may confer antiatherogenic benefit beyond its hypoglycemic action through reduction of coagulation, inflammation, and endothelial dysfunction. Metformin is weight-neutral, but the weight lost by the metformin group and gained by the glipizide group during the trial is unlikely to have played an important role in the outcome.

The practice implications of this high-quality RCT are limited because there is nearly universal consensus that metformin is the drug of first choice in type 2 diabetes. In the UK Prospective Diabetes Study (UKPDS 34), metformin monotherapy was associated with a 36% reduction in all-cause mortality at 10.7 years compared with diet alone. SPREAD-DIMCAD extends the generalizability of UKPDS 34 to high-risk patients.



Tool of the month


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What do I need to tell my patients about hypoglycemia?

Key messages for patients about hypoglycemia include the following recommendations:

  • Review the symptoms of hypoglycemia. Point out that they will not experience all of these symptoms but that they will generally have the same symptoms whenever they are hypoglycemic.
  • Teach the "rule of 15s": Treat with 15 g of carbohydrates, wait 15 minutes and treat with another 15 g of carbohydrates if the blood glucose level is still too low.
  • Caution patients not to overtreat a hypoglycemic episode.
  • Remind patients to always wear identification for diabetes and to test their blood glucose before driving a car or engaging in exercise. The general recommendation is that the blood glucose level should be >100 mg/dL prior to exercise or driving.
  • If patients take medications prone to causing hypoglycemia (insulin or insulin secretagogues), a small carbohydrate snack before engaging in vigorous exercise is reasonable. Remind your patient to recheck blood glucose after exercise to help plan for future exercise sessions.
  • Teach patients to keep glucose tablets or another form of treatment with them at all times (particularly when exercising) and to be sure to keep a form of glucose in the car, purse, briefcase, pocket, gym bag, desk drawer, and nightstand.
  • Make sure that patients at risk for hypoglycemia have a current prescription for glucagon and that someone around them knows how to administer it.
  • Provide information about when to contact clinicians about hypoglycemia (e.g., number of episodes per week, number of severe episodes).
  • Teach patients with hypoglycemia unawareness to recognize neuroglycopenic symptoms early. These patients should have higher targets to avoid hypoglycemia until adrenergic symptoms return.


FDA update


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Single and combo diabetes drugs approved

Alogliptin (Nesina) and two new combination drugs (alogliptin and metformin hydrochloride [Kazano] and alogliptin and pioglitazone [Oseni]) were approved by the FDA to improve blood glucose control in adults with type 2 diabetes, along with diet and exercise.

Alogliptin was demonstrated safe and effective in clinical trials of about 8,500 patients in which it reduced hemoglobin A1c (HbA1c) by 0.4% to 0.6% compared with placebo after 26 weeks of use. The combination of alogliptin/metformin reduced HbA1c 1.1% more than alogliptin alone and 0.5% more than metformin alone after 26 weeks. The alogliptin/pioglitazone combination reduced HbA1c 0.4% to 0.9% more than alogliptin monotherapy and 0.4% to 0.6% more than pioglitazone monotherapy. The FDA is requiring five postmarketing studies: a cardiovascular outcomes trial; an enhanced pharmacovigilance program to monitor for liver abnormalities, serious cases of pancreatitis and severe hypersensitivity reactions; and three pediatric studies. The most common side effects are stuffy or runny nose, headache, and upper respiratory tract infection.


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Incretin mimetics' effects on pancreas under investigation

The FDA is investigating reports of possible increased risk of pancreatitis and precancerous findings of the pancreas from incretin mimetic drugs for type 2 diabetes.

The investigation is based on unpublished new findings based on examination of a small number of pancreatic tissue specimens taken from patients after they died of unspecified causes. The FDA has asked the researchers to provide the methodology used to collect and study these specimens and to provide the tissue samples so the agency can further investigate potential pancreatic toxicity associated with the incretin mimetics. Drugs in the incretin mimetic class include exenatide (Byetta, Bydureon), liraglutide (Victoza), sitagliptin (Januvia, Janumet, Janumet XR, Juvisync), saxagliptin (Onglyza, Kombiglyze XR), alogliptin (Nesina, Kazano, Oseni), and linagliptin (Tradjenta, Jentadueto).

The FDA has not reached any new conclusions about safety risks with incretin mimetic drugs and will communicate its final conclusions and recommendations when the review is complete or when additional information is available to report.



Keeping tabs


.
Spotlight on bariatric surgery

Treatment of type 2 diabetes with bariatric surgery was discussed by several recent publications, including updated guidelines from a group of medical specialty organizations.

The guidelines from the American Society for Metabolic and Bariatric Surgery, the American Association of Clinical Endocrinologists and the Obesity Society expanded the patient population eligible for surgery. Under the new recommendations, patients with diabetes or metabolic syndrome and a body mass index (BMI) of 30 kg/m2 or higher may be offered a bariatric procedure, although the guidelines note that "current evidence is limited" for patients with BMIs under 35. The previous version of the guidelines, from 2008, had found insufficient data to recommend bariatric surgery at a BMI under 35. The updated guidelines were published in the journals Surgery for Obesity and Related Diseases, Endocrine Practice and Obesity on March 26.

Evidence support for bariatric surgery in less obese patients was provided by a report of the Swedish Obese Subjects study. The study included more than 2,000 men and women who underwent bariatric surgery and about 2,000 obese controls receiving usual care. In this report, published in the May Diabetes Care, patients were divided into two groups: those traditionally eligible for bariatric surgery (BMI of 40 or above, or at least 35 with a comorbidity) and noneligible (BMI below 35, or between 35 and 40 with no comorbidities). After up to 20 years of follow-up, researchers found that diabetes incidence was reduced a similar amount (compared to controls) in both the eligible and noneligible groups (73% vs. 67%), leading the study authors to conclude that BMI is not the best criteria for eligibility and that some patients who could benefit from surgery are being excluded.

On the other hand, a very small study of diabetic obese patients undergoing Roux-en-Y gastric bypass found that patients could potentially see as much benefit from caloric restriction as surgery. The 10 study participants first were admitted for 10 days and given a standard liquid preoperative diet, with their glucose measured every four hours. After at least six weeks of washout, they had the surgery, followed by another 10 days of the same liquid diet and glucose measurement. The results, published by Diabetes Care on March 25, showed that patients lost more weight (7.3 kg vs. 4.0 kg) and had lower glycemia (1,293.58 mg/dL per day vs. 1,478.80 mg/dL, reported as area under the curve for daily average capillary glucose measurements) during the presurgery period. The authors speculated the slight difference in overall glycemia is due to the surgery-related stress response. They concluded that "nonsurgical interventions that successfully achieve and maintain such strict caloric restriction have the potential to resolve diabetes to a comparable degree as RYGB."


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MKSAP Answer and Critique



Correct answer: B. Insulin dose reductions.

The correct answer is B. Insulin dose reductions. This item is available to MKSAP 16 subscribers as item 19 in the Endocrinology section. Information about MKSAP 16 is available online.

This patient's dosages of both long-acting and rapid-acting insulin should be decreased by approximately 20%. Hypoglycemia is the major rate-limiting factor in attempting tight glycemic control, especially in patients with type 1 diabetes mellitus. For 48 to 72 hours after a severe episode of hypoglycemia, the body's ability to mount an adrenergic response is blunted, as is the strength of the counterregulatory response. This increases the likelihood of a second severe episode of hypoglycemia that will not be easily recognized (hypoglycemic unawareness), and thus a vicious cycle develops. The best treatment is to reduce the dosage of insulin and scrupulously monitor the blood glucose level for 1 week so that it does not become less than 100 mg/dL (5.6 mmol/L). This intervention allows the brain to reset its adrenergic responses.

Increasing her carbohydrate intake at meals is inappropriate because of her currently healthy diet, her anticipated pregnancy, and the potential for weight gain.

Although α-lipoic acid has shown some efficacy in management of painful diabetic neuropathy, it would have no effect on her hypoglycemic unawareness.

A preprandial injection of pramlintide, a synthetic long-acting analogue of the hormone amylin, is sometimes used in the management of type 1 diabetes to slow down stomach emptying, suppress glucagon secretion, and promote satiety. In this patient, however, pramlintide might actually increase the risk of hypoglycemia.

Switching from insulin glargine to insulin detemir without reducing the dose of insulin is unlikely to be helpful in stopping or reducing this patient's hypoglycemic episodes.

Key Point

  • Hypoglycemia is the major rate-limiting factor in attempting tight glycemic control, especially in patients with type 1 diabetes mellitus.

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