Perspectives and experiences of health care professionals and patients regarding treatments for type 2 diabetes.

BACKGROUND: Several treatment options exist for type 2 diabetes, but little is known about the factors considered by health care providers (HCPs) and patients in Canada in making therapeutic decisions. This study explores perceptions and practices of HCPs and patients related to add-on (i.e., second-line) therapy for type 2 diabetes when initial therapy no longer provides adequate glycemic control. METHODS: HCPs (pharmacists, family physicians, diabetes educators, endocrinologists and nurse practitioners) and patients with type 2 diabetes in Ottawa and Halifax were randomly selected to participate in the study. Phone interviews were conducted with endocrinologists and nurse practitioners and focus groups with the other HCPs and patients. RESULTS AND INTERPRETATION: Sixty HCPs and 14 patients participated in the study. Metformin was consistently reported by prescribers (physicians and nurse practitioners) as the preferred initial therapy. Important factors in choosing second-line therapy (once glycemic control was inadequate with metformin) were antihyperglycemic efficacy, risk of hypoglycemia and weight gain, and long-term safety. Other considerations were cost, insurance coverage and patient preference. There were differences within and between HCP groups in how these other factors were considered and in the perceived advantages and disadvantages of each drug class. Some patients expressed anxiety when second-line agents were prescribed, and others felt poorly informed about treatment options. CONCLUSION: In choosing a second-line therapy for type 2 diabetes, most HCPs placed a high priority on antihyperglycemic efficacy, although there was considerable variability in the relative weight placed on other factors. These findings point to an opportunity for pharmacists to collaborate more actively with other HCPs to ensure that treatment decisions are based on the best available evidence and to educate and involve patients in these decisions.

Choice of therapy in patients with type 2 diabetes inadequately controlled with metformin and a sulphonylurea: a systematic review and mixed-treatment comparison meta-analysis.

BACKGROUND: Metformin and a sulphonylurea are often used in combination for the treatment of type 2 diabetes mellitus. We conducted a systematic review and meta-analysis to evaluate the comparative safety and efficacy of all available classes of antihyperglycemic therapies in patients with type 2 diabetes inadequately controlled with metformin and sulphonylurea combination therapy. METHODS: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, BIOSIS Previews, PubMed and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials published in English from 1980 to November 2009. Additional citations were obtained from the grey literature and conference proceedings and through stakeholder feedback. Two reviewers independently selected the studies, extracted the data and assessed risk of bias. Key outcomes of interest were hemoglobin A1c, body weight, hypoglycemia, patients' satisfaction with treatment, quality of life, long-term diabetes-related complications, withdrawals due to adverse events, serious adverse events and mortality. Mixed-treatment comparison meta-analyses were conducted to calculate mean differences between drug classes for changes in hemoglobin A1c and body weight. When appropriate, pairwise meta-analyses were used to estimate differences for other outcomes. RESULTS: We identified 33 randomized controlled trials meeting the inclusion criteria. The methodologic quality of the studies was generally poor. Insulins (basal, biphasic, bolus), dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) analogues and thiazolidinediones (TZDs) all produced statistically significant reductions in hemoglobin A1c in combination with metformin and a sulphonylurea (-0.89% to -1.17%), whereas meglitinides and alpha-glucosidase inhibitors did not. Biphasic insulin, bolus insulin, and TZDs were associated with weight gain (1.85-5.00 kg), whereas DPP-4 inhibitors and alpha-glucosidase inhibitors were weight-neutral, and GLP-1 analogues were associated with modest weight loss. Treatment regimens containing insulin were associated with increased hypoglycemia relative to comparators, but severe hypoglycemia was rare across all treatments. INTERPRETATION: Third-line agents for the treatment of type 2 diabetes are similar in terms of glycemic control but differ in their propensity to cause weight gain and hypoglycemia. Longer-term studies with larger sample sizes are required to determine if any of the drug classes are superior with regard to reducing diabetes-related complications.

Second-line therapy in patients with type 2 diabetes inadequately controlled with metformin monotherapy: a systematic review and mixed-treatment comparison meta-analysis.

BACKGROUND: Although there is general agreement that metformin should be used as first-line pharmacotherapy in patients with type 2 diabetes, uncertainty remains regarding the choice of second-line therapy once metformin is no longer effective. We conducted a systematic review and meta-analysis to assess the comparative safety and efficacy of all available classes of antihyperglycemic therapies in patients with type 2 diabetes inadequately controlled on metformin monotherapy. METHODS: MEDLINE, EMBASE, BIOSIS Previews, PubMed and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials published in English from 1980 to October 2009. Additional citations were obtained from grey literature and conference proceedings and through stakeholder feedback. Two reviewers independently selected studies, extracted data and assessed risk of bias. Key outcomes of interest were hemoglobin A1c, body weight, hypoglycemia, quality of life, long-term diabetes-related complications, serious adverse drug events and mortality. Mixed-treatment comparison and pairwise meta-analyses were conducted to pool trial results, when appropriate. RESULTS: We identified 49 active and non-active controlled randomized trials that compared 2 or more of the following classes of antihyperglycemic agents and weight-loss agents: sulfonylureas, meglitinides, thiazolidinediones (TZDs), dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) analogues, insulins, alpha-glucosidase inhibitors, sibutramine and orlistat. All classes of second-line antihyperglycemic therapies achieved clinically meaningful reductions in hemoglobin A1c (0.6% to 1.0%). No significant differences were found between classes. Insulins and insulin secretagogues were associated with significantly more events of overall hypoglycemia than the other agents, but severe hypoglycemia was rarely observed. An increase in body weight was observed with the majority of second-line therapies (1.8 to 3.0 kg), the exceptions being DPP-4 inhibitors, alpha-glucosidase inhibitors and GLP-1 analogues (0.6 to -1.8 kg). There were insufficient data available for diabetes complications, mortality or quality of life. INTERPRETATION: DPP-4 inhibitors and GLP-1 analogues achieved improvements in glycemic control similar to those of other second-line therapies, although they may have modest benefits in terms of weight gain and overall hypoglycemia. Further long-term trials of adequate power are required to determine whether newer drug classes differ from older agents in terms of clinically meaningful outcomes.

Efficacy of self-monitoring of blood glucose in patients with type 2 diabetes mellitus managed without insulin: a systematic review and meta-analysis.

BACKGROUND: Self-monitoring of blood glucose levels is commonly performed by patients with diabetes mellitus. However, there is debate surrounding the clinical utility and cost-effectiveness of this practice among patients with type 2 diabetes managed without insulin. We conducted a systematic review and meta-analysis to determine the effect of self-monitoring versus no self-monitoring, and the optimal frequency of self-monitoring, in this population. METHODS: MEDLINE, EMBASE, BIOSIS Previews, CINAHL and PsycINFO were searched for randomized controlled trials (RCTs) and observational studies published in English from January 1990 to March 2009. Additional citations were obtained through searches of the Internet and conference proceedings, and from stakeholder feedback. Two reviewers independently selected studies, extracted data and performed an assessment of the methodologic quality of the studies. Key outcomes of interest were hemoglobin A1c (HbA(1c)) concentration, hypoglycemia, quality of life, long-term complications of diabetes and death. Where appropriate, we pooled data using random-effects meta-analysis. RESULTS: We identified 1624 citations through the literature search and selected 25 articles for inclusion. We observed a statistically significant improvement in the HbA(1c) concentration across RCTs that compared self-monitoring of blood glucose levels with no self-monitoring among patients taking oral antidiabetes drug therapy (weighted mean difference --0.25%, 95% confidence interval -0.36% to -0.15%). Subgroup analysis indicated that results from RCTs that provided patients with education on how to interpret and apply self-monitoring test results were similar to those from RCTs that did not. On the basis of limited evidence, self-monitoring of blood glucose levels did not demonstrate consistent benefits in terms of quality of life, patient satisfaction, prevention of hypoglycemia or long-term complications of diabetes, or reduction of mortality. There was insufficient evidence pertaining to the optimal frequency of self-monitoring. INTERPRETATION: Self-monitoring of blood glucose levels was associated with a modest, statistically significant reduction in hemoglobin A1c concentrations, regardless of whether patients were provided with education on how to interpret and use the test results. Further studies are required to determine whether self-monitoring reduces the risk of long-term complications of diabetes and to identify patients most likely to benefit from self-monitoring.

Efficacy and safety of insulin analogues for the management of diabetes mellitus: a meta-analysis.

BACKGROUND: Although insulin analogues are commonly prescribed for the management of diabetes mellitus, there is uncertainty regarding their optimal use. We conducted meta-analyses to compare the outcomes of insulin analogues with conventional insulins in the treatment of type 1, type 2 and gestational diabetes. METHODS: We updated 2 earlier systematic reviews of the efficacy and safety of rapid-and long-acting insulin analogues. We searched electronic databases, conference proceedings and "grey literature" up to April 2007 to identify randomized controlled trials that compared insulin analogues with conventional insulins. Study populations of interest were people with type 1 and type 2 diabetes (adult and pediatric) and women with gestational diabetes. RESULTS: We included 68 randomized controlled trials in the analysis of rapid-acting insulin analogues and 49 in the analysis of long-acting insulin analogues. Most of the studies were of short to medium duration and of low quality. In terms of hemoglobin A1c, we found minimal differences between rapid-acting insulin analogues and regular human insulin in adults with type 1 diabetes (weighted mean difference for insulin lispro: -0.09%, 95% confidence interval [CI] -0.16% to -0.02%; for insulin aspart: -0.13%, 95% CI -0.20% to -0.07%). We observed similar outcomes among patients with type 2 diabetes (weighted mean difference for insulin lispro: -0.03%, 95% CI -0.12% to -0.06%; for insulin aspart: -0.09%, 95% CI -0.21% to 0.04%). Differences between long-acting insulin analogues and neutral protamine Hagedorn insulin in terms of hemoglobin A1c were marginal among adults with type 1 diabetes (weighted mean difference for insulin glargine: -0.11%, 95% CI -0.21% to -0.02%; for insulin detemir: -0.06%, 95% CI -0.13% to 0.02%) and among adults with type 2 diabetes (weighted mean difference for insulin glargine: -0.05%, 95% CI -0.13% to 0.04%; for insulin detemir: 0.13%, 95% CI 0.03% to 0.22%). Benefits in terms of reduced hypoglycemia were inconsistent. There were insufficient data to determine whether insulin analogues are better than conventional insulins in reducing long-term diabetes-related complications or death. INTERPRETATION: Rapid-and long-acting insulin analogues offer little benefit relative to conventional insulins in terms of glycemic control or reduced hypoglycemia. Long-term, high-quality studies are needed to determine whether insulin analogues reduce the risk of long-term complications of diabetes.

Potential interactions between pharmaceuticals and natural health products in Canada.

This study sought to measure the extent to which potentially interacting combinations of natural health products (NHPs) and drugs are used in the Canadian adult population. Data were obtained from the Statistics Canada 2000-2001 National Population Health Survey. A total of 11 424 adults completed the survey. Of the survey participants, 9.3% reported the use of at least 1 natural health product in the prior 2 days. Among natural health product users, 57% also used a conventional medicine with systemic exposure in the same time period. A minimum of 1 potential drug-NHP interaction was identified in 28.4% of such combination users. Most interactions (90%) were of unknown clinical significance. Female gender, older age, lower education, and the presence of diabetes and high blood pressure were associated with a higher risk of having at least 1 potential interaction. Health professionals need to maintain a working knowledge of common potential drug-NHP interactions, to dialogue with all patients regarding the use of natural health products, and to remain vigilant in reporting all suspected interactions and adverse events involving natural health products. Regulatory agencies should also capture and assess reports of drug-NHP interactions more effectively.

Natural health product use in Canada: analysis of the National Population Health Survey.

BACKGROUND: The use of natural health products (NHPs) in Western countries has increased dramatically over the past two decades. Although prevalence estimates have been published in the U.S. and elsewhere, little is known about the characteristics of persons who use NHPs. OBJECTIVES: To measure the prevalence of NHP use among adults in Canada, identify the most commonly used agents, and determine the socioeconomic, demographic, and health-related correlates of use. METHODS: NHP use by adults was assessed using the 2000-2001 National Population Health Survey (NPHS), a biennial general health survey conducted by Statistics Canada. A total of 11,424 adults completed the survey in 2000-2001. NHPs were defined as botanical and naturally-derived non-botanical products, excluding essential vitamins and minerals. Prevalence of use estimates were calculated nationally, and by age, gender, socioeconomic status, disease states, and health care practices. Multivariate logistic regression modeling was used to simultaneously assess the correlations of these variables with NHP use. RESULTS: The prevalence of past 2-day NHP use in Canada was 9.3% in 2000-2001. Fifty-seven percent of users also reported taking a conventional medicine in the same period. Glucosamine, echinacea, and garlic were the most frequently used products. Women reported NHP use more frequently than men (11.5% vs. 7.1%). As compared to young adults, NHP use was about 50% higher in middle-aged and older Canadians. There were no associations with either income or education level. Several disease states were associated with a high prevalence of NHP use: respondents with fibromyalgia (23.3%), inflammatory bowel disease (17.4%), and urinary incontinence (16.8%) were most likely to be NHP users. However, in the multivariate analysis, age and the use of vitamins or minerals were most predictive of NHP use, while health status variables were of less importance. CONCLUSIONS: NHP use is an important health phenomenon in Canada. Although respondents in poor health were more likely to use NHPs, a significant proportion of healthy Canadians also reported NHP use. The use of NHPs also cut across different socioeconomic groups. Concurrent use of conventional medications was common and suggests a need for health professionals to monitor for potential interactions.