American Diabetes Association (ADA) 71st Scientific Sessions

June 24-28, 2011; San Diego, CA
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Poster

Hypoglycemia Risks, Costs Associated With Type 2 Diabetes Treatments

San Diego, CA—A retrospective analysis of claims for 212,061 patients (56% male) with type 2 diabetes found that those taking sulfonylureas, insulin, or other oral antidiabetic agents (eg, meglitinide and alpha-glucosidase) had a higher 6-month risk of hypoglycemia than patients taking metformin or thiazolidinediones. Use of dipeptidyl peptidase-4 inhibitors or exenatide were not found to increase hypoglycemia risk. Findings were presented in a poster at the recent ADA meeting.

The authors noted that two prior studies have shown that patients who experience hypoglycemia while taking antidiabetic medication are less satisfied with their therapy and are therefore less likely to adhere to it than those who do not develop hypoglycemia, making treatment less effective.

Investigators for the current study reviewed records for adults with type 2 diabetes from the Ingenix Impact database, which contains enrollment and demographic information and prescription drug claims for 45 US health plans. Patients who experienced hypoglycemia with antidiabetic therapy racked up significantly higher annual drug and medical costs than patients who experienced no hypoglycemia ($14,031 vs $9007, respectively; P <.0001). An analysis of just the diabetes-related drug and medical claims showed that these were also significantly higher each year among patients experiencing hypoglycemia as compared with those who did not ($7012 vs $3265, respectively; P <.0001).

The authors analyzed data pertaining to a subset of 31,109 elderly patients (aged ≥65 years) and found that they had higher all-cause and diabetes-related annual costs and a greater risk of hypoglycemia compared with the cohort of individuals aged 18 to 65 years. Annual drug and medical costs for the elderly population totaled $20,264 for patients experiencing hypoglycemia versus $11,897 for those who did not develop the condition. The portion of annual costs related to diabetes totaled $11,829 in the hypoglycemia group versus $4190 in the group with no hypoglycemia.

Certain drugs were associated with significantly higher 6-month hypoglycemia risk overall (P <.0001 for each comparison): insulin (hazard ratio [HR], 2.10; 95% confidence interval [CI], 1.98-2.24); other oral antidiabetic agents (HR, 1.59; 95% CI, 1.46-1.74); sulfonylureas (HR, 1.56; 95% CI, 1.50-1.62); metformin (HR, 1.18; 95% CI, 1.13-1.23); and thiazolidinediones (HR, 1.09; 95% CI, 1.04-1.13).

In elderly patients, the following treatments were significantly associated with higher hypoglycemia risk over 6 months (P <.0001 for each comparison): insulin (HR, 2.36; 95% CI, 2.04-2.74); other oral antidiabetic agents (HR, 1.86; 95% CI, 1.57-2.21); sulfonylureas (HR, 1.95; 95% CI, 1.78-2.14); and thiazolidinediones (HR, 1.22; 95% CI, 1.11-1.35).

Individuals eligible for study inclusion had at least two independent claims for type 2 diabetes and no claims for type 1 diabetes between January 1999 and September 2008. They  were also required to have filled at least one prescription for an oral antidiabetic agent and to have been continuously enrolled in a medical and pharmacy benefits plan for 12 months after filling their first antidiabetic prescription. One-third of eligible patients were enrolled in a health maintenance organization, ~40% were enrolled in a point-of-service health plan, and 26.3% subscribed to a preferred provider organization.

The study did not directly compare data for elderly versus nonelderly patients. The authors hope to do this in the future.

This study was sponsored by Takeda Pharmaceuticals International, Inc.
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Lifestyle Interventions Improve Glycemic Control for Patients With Type 2 Diabetes

San Diego, CA—A multicenter, randomized trial involving patients with type 2 diabetes showed that intensive dietary intervention through consultations with a dietician and nurse demonstrated significantly improved glycemic control compared with standard care. Adding an exercise regimen to the dietary changes, however, did not correlate with further improvement. Results of the Early ACTID (Activity in Type 2 Diabetes) trial were presented at the ADA meeting and simultaneously published online in The Lancet.

From December 2005 through September 2008, the investigators enrolled 593 residents of southwest England, aged 30 to 80 years, who had received a diagnosis of type 2 diabetes in the previous 5 to 8 months. Exclusion criteria included a glycated hemoglobin A_1c (HbA_1c) level of >10%, a blood pressure reading of >180/100 mm Hg, a body mass index (BMI) of <25 kg/m², and weight of >180 kg.

Patients were randomized at a 2:5:5 ratio to the following interventions: normal care, where standard dietary and exercise advice were provided at randomization and again at the study’s conclusion, with reviews by a physician and nurse at baseline, 6 months, and
12 months; intensive diet, involving a 1-hour consultation with a dietician at randomization and a 30-minute session every 3 months, along with nine 30-minute consultations with a nurse during the study; and intensive diet plus exercise, which required the patient to take a brisk, 30-minute walk on at least 5 days of each week, tracked by a pedometer and diaried. During the 12-month period, patients assigned to the diet cohort and the diet-plus-exercise group consulted with a dietician for 2 more hours and with a nurse for 4.5 more hours than the patients who were randomized to receive normal care.

The arms were well balanced in terms of baseline demographics. Approximately 65% of patients were men and the vast majority (95%) were white. The approximate mean age of the patients was 60 years.

At 12-month follow-up, patients in the diet group and the diet-plus-exercise group had significantly improved HbA_1c levels compared with patients in the normal care group (P = .005 and
P = .027, respectively). The mean HbA_1c level increased by 0.09% in the normal care group, decreased by 0.09% in the diet group, and decreased by 0.04% in the diet-plus-exercise group. No statistically significant difference was observed, however, in HbA_1c change between the diet and diet-plus-exercise groups (P = .43).

In addition, none of the groups differed significantly in mean systolic or diastolic blood pressure readings or in mean levels of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides at study end. Compared with patients in the normal care group, those assigned to the diet group and the diet-plus-exercise group demonstrated significant weight loss (P <.0001 for both comparisons) and a significant decline in BMI (P <.0001 for both comparisons).

Robert C. Andrews, MB, ChB, PhD, was the study’s lead author, and he offered possible explanations for why exercise did not contribute to better patient outcomes. He said that the authors might have selected the wrong activity and that perhaps the exercise regimen should have included aerobic and anaerobic activities. He also hypothesized that people who exercise are not as strict with their dietary intake. He wondered whether, if instead of focusing solely on increasing the patients’ activity levels, the researchers should have concentrated more on decreasing the amount of time that the patients spent being sedentary.

Despite finding no additional benefit from combining exercise with dietary changes, he said, “We should concentrate on exercise and diet.” The study’s message, he added, was not that patients should avoid exercise.
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Cost Results From the Look AHEAD Study

San Diego, CA— The annual costs associated with managing patients with type 2 diabetes through a structured lifestyle intervention decreased during a 4-year period, according to the results of an ongoing multicenter, randomized controlled trial. Ping Zhang, PhD, from the Centers for Disease Control and Prevention’s Division of Diabetes Translation, presented the findings at the recent ADA meeting in an oral abstract session.

The Look AHEAD (Action for Health in Diabetes) study enrolled 5145 overweight patients with type 2 diabetes and randomly assigned them at a 1:1 ratio to an intensive lifestyle intervention program (n = 2570) or a control group, where patients received a diabetes support and education program (n = 2575). The study, sponsored by the Department of Health and Human Services and the National Institute of Diabetes and Digestive and Kidney Diseases, plans to follow the patients for up to 13.5 years.

The trial is examining the long-term effects of decreasing caloric intake and increasing physical activity on cardiovascular morbidity and mortality. Eligible individuals were between 45 and 76 years of age, had a body mass index (BMI) of ≥25 kg/m² or ≥27 kg/m² if they were taking insulin, had a glycated hemoglobin A_1c level of ≤11%, had a blood pressure reading of ≤160/100 mm Hg, and had a triglyceride level of ≤600 mg/dL.

The two groups had similar baseline characteristics. Each consisted of approximately 60% women and 37% minorities, the average age was approximately 59 years, the average BMI was approximately 36.0 kg/m², approximately 15% used insulin, and approximately 15% had a history of cardiovascular disease.

Zhang said that structured lifestyle interventions have proven effective for preventing and managing type 2 diabetes. In this trial, the researchers were hoping to see a 7% weight loss for the lifestyle intervention group, whereas participants had a goal of losing 10% of their body weight. People were instructed to spend 175 minutes per week on activities with moderate intensity.

During the first 6 months, the lifestyle intervention group attended weekly meetings (three group meetings and one individual meeting per month). From months 7 through 12, patients attended two group sessions and one individual session monthly. In years 2, 3, and 4, they had a monthly individual counseling session and refresher courses or campaigns two or three times per year. Patients given diabetes support education had three to four meetings annually on topics such as diet, exercise, and social support.

The authors estimated the average clinic-specific personnel cost of a patient visit and had the study’s staff complete questionnaires detailing the types of personnel and time involved for individual and group sessions. Research costs were excluded from the calculations. Each site also reported the salaries and benefits associated with each type of worker.

In year 1, the average cost per participant assigned to the lifestyle intervention group was $3175. The cost decreased to $1760 per participant in year 2, to $1214 per participant in year 3, and to $1176 per participant in year 4. Meanwhile, the average cost per participant assigned to the diabetes support education group was $83 in the first year, $64 in the second year, $65 in the third year, and $72 in the fourth year.

Zhang said that the data presented at the ADA meeting will be combined with other cost data, such as expenses related to laboratory testing, food, and exercise, to determine the cost-effectiveness of implementing the lifestyle intervention program.

According to Zhang, the following companies were major study donors: Abbott Nutrition, FedEx Corp, Health Management Resources, Hoffmann-La Roche, Inc, LifeScan, Inc, Nestlé HealthCare Nutrition, Inc, and Unilever.
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Poster

Adding Exenatide to Glucose-Lowering Regimens Reduces Heart Failure Risk

San Diego, CA—A retrospective analysis of data from an electronic medical records database found that adding twice-daily injections of exenatide to a glucose-lowering regimen for patients with type 2 diabetes was associated with a reduced risk of heart failure. Results of the analysis were presented at the ADA meeting in a poster titled The Risk of Heart Failure among Patients Receiving Exenatide Versus Other Glucose-Lowering Medications for Type 2 Diabetes: A Matched Retrospective Cohort Analysis of the GE Healthcare Electronic Medical Record Database.

In 2005, exenatide became the first glucagon-like, peptide-1 receptor to receive US Food and Drug Administration approval as a treatment for patients with type 2 diabetes. Exenatide is not recommended to be used to replace insulin therapy, nor is it intended to be  used with insulin, according to a news release from the manufacturers of the drug (Amylin Pharmaceuticals, Inc, and Eli Lilly and Company).

Study investigators analyzed data obtained from the national Medical Quality Improvement Consortium, which consists of more than 14,000 healthcare providers that use GE Healthcare’s Centricity electronic medical records system. They identified 778,408 patients with a diagnosis of type 2 diabetes who had received glucose-lowering treatment (ie, exenatide, insulin, and/or another therapy) between January 2005 and September 2010.

The authors randomly matched the patients who took exenatide 1:1 with those who had not taken the drug, pairing them based on sex, age (according to 10-year spans), follow-up time available, and thiazolidinedione use. Patients were considered to have experienced heart failure if they had documented evidence of having had elevated concentrations (>100 pg/mL) of brain natriuretic peptide in addition to a clinical diagnosis of heart failure.

In an analysis of 50,330 patients, with disease severity adjusted according to the weighted Charlson Comorbidity Index (CCI), those who took exenatide with insulin and another antidiabetic therapy were 57% less likely to develop heart failure than those who took insulin and another antidiabetic therapy, but who did not use exenatide (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.35-0.53). When not adjusting for disease severity according to the weighted CCI, the OR dropped to 0.41 (95% CI, 0.34-0.51).

In an analysis of 53,446 patients, again after adjusting for disease severity using the weighted CCI, those individuals who received exenatide and other noninsulin therapies were 31% less likely to develop heart failure compared with those patients who took other noninsulin therapies but had not taken exenatide (OR, 0.69; 95% CI, 0.44-1.07). The unadjusted OR and 95% CI were found to be the same as the adjusted findings.

When combining data for all the patients (n = 103,776) with type 2 diabetes, the patients who took exenatide were 54% less likely to develop heart failure compared with those who had not received exenatide (OR, 0.46; 95% CI, 0.38-0.56). The authors noted that the results of the study were “consistent with the positive effects of exenatide on cardiovascular risk factors observed in the clinical development program for exenatide and in clinical practice.”

This analysis was funded by Amylin Pharmaceuticals, Inc, and Eli Lilly and Company.  
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Poster

Substituting Liraglutide for Sitagliptin Is Effective in Patients With Type 2 Diabetes

San Diego, CA—A randomized trial that switched patients with type 2 diabetes from sitagliptin to liraglutide reported improved glycemic control and weight loss after 26 weeks. In addition, the percentage of patients achieving the ADA’s target glycated hemoglobin A_1c (HbA_1c) level of <7% increased from 30% to 50%. Both drugs are approved by the US Food and Drug Administration as treatments for type 2 diabetes. Trial data were presented at the ADA meeting during a poster session.

The 26-week study served as an extension of a 52-week randomized, parallel-group, open-label trial that had compared 1.2- and 1.8-mg doses of liraglutide with a 100-mg dose of sitagliptin in patients with type 2 diabetes mellitus. The oral drugs were administered daily in combination with metformin. Patients in the liraglutide groups experienced a significantly greater reduction in levels of HbA_1c and fasting plasma glucose, and they lost significantly more weight.

Eligible participants were 18 to 80 years of age, with an HbA_1c level between 7.5% and 10.0%. Their body mass index had to be ≤45 kg/m² and they had to have been taking ≥1500 mg of metformin daily for ≥3 months.

A total of 436 patients completed the initial 52-week trial, and 419 of these individuals continued on to the 26-week extension phase. In total, 381 persons completed all 78 weeks of the study.

In the extension phase, the patients who had initially been assigned to the sitagliptin group were switched at a 1:1 ratio to receive either a 1.2-mg dose or a 1.8-mg dose of liraglutide. Patients who had been switched to the 1.2-mg dose of liraglutide experienced a mean decrease of 0.24% in HbA_1c levels (P = .006), whereas those patients who had been switched to the 1.8-mg dose of liraglutide experienced a mean decrease in HbA_1c  levels of 0.45% (P = .0001).

The authors said that 29.5% of patients who were switched to 1.2 mg of liraglutide for the study’s extension phase had achieved an HbA_1c level of <7% at the end of the study’s
52-week main phase. This increased to 49.2% of patients at the conclusion of the extension study. From week 52 to week 78, the average fasting plasma glucose level for this contingent of patients decreased by a mean of 0.84 mmol/L (P = .0004)

Among patients who switched to 1.8 mg of liraglutide, 29.5% had an HbA_1c level of <7% at 52 weeks compared with 50.0% of patients at 78 weeks. Fasting plasma glucose levels fell a mean of 1.42 mmol/L from week 52 to week 78 for those who switched to 1.8 mg of liraglutide (P < .0001). Both groups experienced a significant decrease in mean body weight. Patients who switched to 1.2 mg of liraglutide lost a mean of 1.64 kg (P <.0001), and those who switched to 1.8 mg of liraglutide lost a mean of 2.48 kg (P <.0001).

Satisfaction was assessed by comparing Diabetes Treatment Satisfaction Questionnaire scores from week 52 to week 78. Scores increased from a mean of 31.9 to 33.3 for patients who switched to 1.2 mg of liraglutide and from 30.9 to 31.7 for patients who switched to 1.8 mg of liraglutide, which was not significant.

Serious adverse events occurred in 6.0% of patients who switched to 1.2 mg of liraglutide and 2.9% of patients who switched to 1.8 mg of the drug. Gastrointestinal disorders were the most common adverse event, affecting >30% of patients.

This study was supported by Novo Nordisk.