Hypoglycemic events and glycosylated hemoglobin values in patients with type 2 diabetes mellitus newly initiated on insulin glargine or premixed insulin combination products.

PURPOSE: Rates of hypoglycemic events and their associated costs were compared among patients with type 2 diabetes mellitus newly initiated on insulin glargine or a premixed insulin fixed-combination product. METHODS: Patients newly initiated on insulin glargine or premixed insulin fixed-combination products (including pen delivery systems) between June 1, 2001, and February 29, 2004, were identified using an administrative claims database. Hypoglycemic events were identified from International Classification of Diseases, 9th Revision, Clinical Modification codes. Multivariate analyses were performed. RESULTS: A total of 2315 patients met the inclusion criteria. Of those, 1212 received insulin glargine and 1103 received a premixed fixed-combination insulin product. The mean +/- S.D. treatment duration was 13.7 +/- 8.1 months. Patients treated with premixed insulin had a higher hypoglycemic event rate than glargine patients (13.8 versus 7.0/100 patients/year; p = 0.027), which yielded a number needed to treat of 15 patients. The mean cost per hypoglycemic event was $1049 (95% confidence interval, $426-1672). The mean annual cost of all insulin use was $46 more for the insulin glargine cohort than for those who received premixed insulin ($534 versus $488, respectively) (p < 0.05). Mean postindex insulin use was higher in patients receiving premixed insulin than in those treated with insulin glargine (48.1 versus 43.8 units per day) (p < 0.05). CONCLUSION: Patients with type 2 diabetes mellitus who were newly initiated on insulin glargine had a lower rate of hypoglycemic events compared with patients newly initiated on a premixed fixed-combination insulin product. Treatment of 15 patients with insulin glargine instead of premixed insulin for one year would avoid one hypoglycemic event per year.     

Budget impact of treating commercially insured type 1 and type 2 diabetes patients in the United States with insulin degludec compared to insulin glargine

Objective: To quantify the annual budget impact if all US commercially insured type 1 diabetes mellitus patients on basal–bolus therapy (T1DM_BBT), type 2 diabetes mellitus patients on basal–oral therapy (T2DM_BOT), and type 2 diabetes mellitus patients on basal–bolus therapy (T2DM_BBT) switched from insulin glargine (IGlar) to insulin degludec (IDeg).

Methods: A short-term (1 year) budget impact model was developed to evaluate the costs of IDeg vs. IGlar in three treatment groups (T1DM_BBT, insulin-naïve T2DM_BOT, and T2DM_BBT) through a simulation for a potential US health plan population of 35 million. The analysis captured direct medical costs associated with insulin treatment (insulin, needles, and self-monitored glucose testing) and costs related to managing hypoglycemic episodes. There were a total of 59,780 T1DM_BBT patients, 383,145 T2DM_BOT patients, and 171,325 T2DM_BBT patients expected to be using long-acting insulin. A sensitivity analysis on the entire US population was also conducted.

Results: Among T1DM_BBT patients, IDeg was associated with an annual cost savings of ?$357.13 per patient per year (PPPY), driven primarily by reduced insulin utilization. IDeg was also found to be cost saving among T2DM_BOT patients (?$1206.61 PPPY), driven primarily by reductions in the cost of treating severe hypoglycemic episodes. Among T2DM_BBT patients, IDeg was associated with an additional cost to the plan of $1420.04 PPPY; however, this result was driven by a higher insulin dose for IDeg compared to IGlar. Overall, IDeg demonstrated cost savings of $240 million per year, which accounted for total cost savings of 3.5% vs. IGlar.

Conclusions: The results of this analysis suggest that the reduced insulin utilization and fewer hypoglycemic episodes associated with IDeg may translate into reduced costs for payers. The model is limited by simplification of a complex disease state and assumptions surrounding disease state, treatment patterns, and costs. Therefore, results may not accurately reflect actual health plans or real-world practice patterns.     

Insulin glargine added to therapy with oral antidiabetic agents improves glycemic control and reduces long-term complications in patients with type 2 diabetes - a simulation with the Diabetes Mellitus Model (DMM)

OBJECTIVE: The purpose of this study was to compare the effect of two insulin therapies with respect to long-term complications in type 2 diabetes patients using the Diabetes Mellitus Model (DMM). The therapies under investigation were insulin glargine combined with the oral antidiabetic agents, glimepiride and metformin, (BOT = basal supported oral treatment) and premixed insulin (CT = conventional therapy). METHODS: The DMM predicts complications over a 10-year period using data from published studies. Particular interest is placed on the influence of HbA1c levels related to time. The simulations are based on 10,000 virtual patients taking BOT and CT and the clinical data are based on the results of the LAPTOP study (Lantus + Amaryl + metformin versus premixed insulin in patients with type 2 diabetes mellitus after failing oral treatment pathways) comparing BOT and CT for 24 weeks. The simulations were performed in patients aged 60 A+/- 9 years with type 2 diabetes in which the duration of disease had a baseline of 9 A+/- 7 years. Sensitivity analyses were carried out by changing the response rate of those on BOT, the age of patients and duration of diabetes. RESULTS: The overall relative risk reductions obtained with BOT versus CT for the base case are, 11% for the nervous and vascular systems, 7% for the renal system, 5% for ophthalmic disorders, 3% for the cardiovascular system and mortality and 6% for any kind of event after 10 years. The advantages of BOT were robust to all the changes in the sensitivity analyses. When compared with the base case, the best therapeutic effects were obtained in younger patients who had been diabetic for a shorter period. CONCLUSIONS: Using the DMM data from the LAPTOP study, simulations based on both therapies showed that the BOT regimen provides better glycemic control and reduction in HbA1c thereby leading to a reduction in the long-term complications of diabetes and mortality.     

Patient-level estimates of the cost of complications in diabetes in a managed-care population

OBJECTIVE: To develop incidence-based estimates of the cost of several diabetes-related complications. DESIGN AND SETTING: This was a retrospective cohort study in a large health maintenance organisation. A total of 8905 patients with type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus and 36,520 age- and gender-matched controls without diabetes were observed from 1992 to 1995. Incidence rates of 6 major diabetes-related complications were computed for both populations. Annual health expenditures in the first and second year following diagnosis were computed for each complication. For comparison, annual costs were derived for individuals without diabetes or the complication of interest. MAIN OUTCOME MEASURES AND RESULTS: Over 3 years of observation, incidence rates for the groups with and without diabetes were as follows: myocardial infarction 9.0 versus 3.2%; stroke 8.7 versus 3.8%; hypertension 26.2 versus 16.9%; end-stage renal disease 5.9 versus 1.4%; foot ulcer 7.9 versus 1.1%; and eye disease 44.3 versus 2.8%. Expressed as a multiple of the average annual cost of care for those without diabetes [$US3400/year (1995 dollars) for those over 65 years of age] and the related complication of interest, excess expenditures for those with diabetes were as follows for the first year following diagnosis: no complications 1.59; myocardial infarction 4.1; stroke 3.5; hypertension 2.56; end-stage renal disease 4.32; foot ulcer 4.0; and eye disease 2.46. For younger cohorts (less prevalent in the sample), incremental costs for each complication were generally greater than in the older group. CONCLUSIONS: The high incidences and costs may support the value of aggressive early intervention for patients with diabetes. These data will be useful for pharmacoeconomic modelling of the cost effectiveness of new and existing therapies for this condition.     

Management of diabetes mellitus medications in the nursing home

Nursing home staff are well aware of the increasing number of residents who experience diabetes mellitus. These residents consume an inordinate amount of resources and often have major disabilities and co-morbidities. Although nonpharmacological therapies, such as consistent carbohydrate intake and increased activity levels, are always indicated in diabetes management, pharmacological therapies are often necessary to prevent the acute complications of diabetes and delay some of the long-term complications. Residents with type 2 diabetes may be managed with oral antidiabetic agents and insulin, whereas residents with type 1 diabetes will always require insulin. Oral antidiabetic agents include insulin secretagogues, which stimulate endogenous insulin secretion and are most effective in leaner persons with type 2 diabetes. Metformin is another oral antidiabetic agent; this decreases inappropriate hepatic glucose release and is most effective in obese residents with high fasting blood glucose levels. The thiazolidinediones, also called glitazones, are insulin sensitisers that enable peripheral tissues to utilise insulin more effectively. The alpha-glucosidase inhibitors delay intestinal absorption of ingested carbohydrates. In addition to oral antidiabetic agents, insulin is frequently used in diabetes management. Insulin is always indicated in type 1 diabetes and is often necessary for residents with type 2 diabetes to optimise glycaemic control. Insulin can be rapid, fast, intermediate or long acting. In addition, basal insulin is now available. These insulins can be combined with each other and, in type 2 diabetes, with oral antidiabetic agents. In order to use pharmacological therapies appropriately, the glycaemic patterns of nursing home residents should be identified, using capillary blood glucose monitoring. Once these patterns have been identified, nonpharmacological therapies can be used, usually in conjunction with the many oral antidiabetic agents and various insulins available, to optimise glycaemic control in each resident.     

Repaglinide : a pharmacoeconomic review of its use in type 2 diabetes mellitus

Repaglinide (Prandin), NovoNorm, GlucoNorm, an oral insulin secretagogue, was the first meglitinide analogue to become available for use in patients with type 2 diabetes mellitus. The drug lowers postprandial glucose excursions by targeting early-phase insulin release, an effect thought to be important in reducing long-term cardiovascular complications of diabetes. Repaglinide provided similar overall glycaemic control to that achieved with glibenclamide (glyburide), as assessed by glycosylated haemoglobin (HbA(1c)) and fasting blood glucose levels, and was generally well tolerated in well designed clinical trials. Its rapid onset and relatively short duration of action allow for flexible meal schedules. Two modelled US cost-effectiveness analyses projected lifetime costs and outcomes for a hypothetical cohort of patients with type 2 diabetes. Both analyses projected long-term complications using data on HbA(1c) level changes from short-term clinical trials. Repaglinide plus rosiglitazone was dominant over rosiglitazone in one analysis, and repaglinide plus metformin was dominant over nateglinide plus metformin in the other. A similar Canadian analysis showed a favourable incremental cost-effectiveness ratio (相似文献   

Modelling cost effectiveness of insulin glargine for the treatment of type 1 and 2 diabetes in Canada

BACKGROUND AND OBJECTIVE: Intensive insulin therapy improves glycosylated haemoglobin (Hb(A1C)) levels and delays the onset of long-term diabetes-related complications. Current treatment guidelines recommend maintaining a glycosylated haemoglobin (Hb(A1C)) of < or = 7% in patients with type 1 and 2 diabetes mellitus. However, the risk of hypoglycaemia increases with lower Hb(A1C) levels. As such, patients often choose to settle for suboptimal glucose control in order to prevent hypoglycaemic events. At a given Hb(A1C) level, treatment with insulin glargine results in a lower risk of hypoglycaemia in type 1 and 2 diabetes compared with NPH insulin. It has been proposed that the lower hypoglycaemic risk will allow more patients to achieve target Hb(A1C) levels with insulin glargine compared with NPH insulin. The objective of this study was to assess the cost effectiveness of insulin glargine compared with NPH insulin in patients with type 1 or 2 diabetes who had inadequate glycaemic control. METHODS: A long-term, state-transition model was developed to simulate the natural history of type 1 and 2 diabetes. Risks of diabetes-related macro- and microvascular complications and mortality by Hb(A1C) levels were estimated based on the UKPDS (United Kingdom Prospective Diabetes Study). Outcome measures included complication rates and associated costs, insulin costs, life years (LYs) and QALYs. The baseline analysis was conducted for patients with type 1 and 2 diabetes (aged 27 and 53 years, respectively) with Hb(A1C) levels >7%, using a 36-year time horizon and a Canadian public payer perspective. Costs and effects were discounted at 5% per annum. Univariate sensitivity analyses were performed on key model inputs. All costs were reported in $Can (2005 values). RESULTS: The NPH insulin group had lower total costs than the insulin glargine group for patients with inadequately controlled diabetes (Hb(A1C) >7%; lifetime difference 1398 Can dollars and 1992 Can dollars, respectively, in type 1 and 2 diabetes). However, patients treated with insulin glargine had greater total and quality-adjusted life expectancy than those who received NPH insulin (incremental LY = 0.08 and QALYs = 0.07 in type 1 diabetes and incremental LY = 0.25 and QALYs = 0.23 in type 2 diabetes). The weighted incremental cost per LY gained and QALY gained were 18,661 Can dollars and 20,799 Can dollars, respectively, in type 1 diabetes and 8041 Can dollars and 8618 Can dollars, respectively, in type 2 diabetes (discounted results). CONCLUSIONS: The cost-effectiveness ratios for insulin glargine use for type 1 and 2 diabetes provide evidence for its adoption from a Canadian healthcare payer perspective.     

Short-term economic impact of body weight change among patients with type 2 diabetes treated with antidiabetic agents: analysis using claims,laboratory, and medical record data

ABSTRACT

Background: Obesity is highly prevalent among patients with type 2 diabetes. Unfortunately, weight gain may also be a consequence of some antidiabetic medications. Although clinical benefits of weight loss have been established, the economic consequence of weight change among patients with type 2 diabetes is unclear.

Objectives: The objective was to measure 1?year total and diabetes-related health care costs associated with weight change during the preceding 6?month period among type 2 diabetic patients on antidiabetic therapy.

Methods: Administrative claims, electronic laboratory data and medical chart information were abstracted for continuously enrolled adults with type 2 diabetes from an health maintenance organization (HMO) for the period from July 1, 1997 through October 31, 2005. To assess the economic impact of weight change, three regression models were applied to estimate the following: (1) the effect of weight change in general (one-slope model); (2) the different effects of weight gain and no weight gain(two-slope model); and (3) the different effects of weight gain and no weight gain (i.e., no change or weight loss) among obese and non-obese patients (four-slope model). Patients included in the study had a baseline weight measurement and a second weight measurement approximately 6 months later. They were also required to be on at least one antidiabetic drug therapy within 1 month around the baseline weight measurement date (index date). Based on the measured weight change, patients were classified into two groups – weight gainers and non-weight gainer. Total health care cost and diabetes-related cost were measured during the 1?year period following the second weight measurement and were adjusted to 2004 dollars by the medical component of the Consumer Price Index (CPI). Generalized linear models with log link function and gamma distribution were applied to assess the impacts of weight change on the 1?year total health care cost as well as 1?year diabetes-related cost. All models controlled for patients’ baseline demographics, comorbidities, body mass index (BMI), glycosylated hemoglobin (HbA_1c), and prior resource utilization.

Results: The study included 458 patients, of whom 224 (48.9%) experienced minimum weight gain of 1?pound between the two weight measurements. The average 1?year total health care cost following the second weight measure was $6382 and the diabetes-related cost was $2002. The mean total health care cost was $7260 for the weight-gainers and $5541 for the non-weight gainers (?p = 0.046), and the mean diabetes-related cost, respectively, was $2141 and $1869 (?p = 0.006). Results from the models showed that one percentage point of weight change was positively associated with a 3.1% ($213, p < 0.01) change in total health care cost. When weight gain and no gain were modeled separately, one percentage point of weight loss was associated with a 3.6% ($256, p < 0.05) decrease in total health care cost and a 5.8% ($131, p < 0.01) decrease in diabetes-related cost. However, one percentage point of weight gain was not associated with significant increase in either total health care or diabetes-related cost. Further, results from the model with interactions between weight change and obesity status revealed that the economic benefit of weight loss was more pronounced in the obese group (BMI ≥ 30). Log likelihood ratio tests showed that the one-slope model for total health care cost and the two-slope model for diabetes-related cost are the appropriate models of choice.

Conclusions: Weight loss significantly reduced diabetes-related costs. Controlling for baseline factors in the regression model, the 1?year total health care cost following 1% weight loss (or gain) was $213 cost decrease (or increase). Diabetes-related cost did not appear to be associated with weight gain. Economic benefit of weight loss was evident among type 2 diabetic patients on antidiabetic therapy, especially among obese patients.     

Prevalence and antihyperglycemic prescribing trends for patients with type 2 diabetes in Italy: A 4-year retrospective study from national primary care data

To estimate the prevalence of type 2 diabetes in Italy and to investigate patient-related variables associated with the use of different antihyperglycemic therapies. This study was conducted between the years 2000-2003 from a source population comprising a cumulative sample of 394,719 patients from 320 General Practitioners across Italy, who provide information to the Health Search/Thales Database (HSD). A total sample of 23,729 of patients with type 2 diabetes age 15 years or older was selected from the source population. During the study years, the prevalence of type 2 diabetes increased from 4.7 to 6.0%. A significant increase in the use of antihyperglycemic therapy was also observed between 2000 and 2003. In particular, the use of biguanides increased. During the same period, the use of sulfonylurea monotherapy, oral combination therapy and insulin with oral combination therapy decreased. The results from the multivariate analysis revealed that healthier patients were more likely to be prescribed biguanide and sulfonylurea monotherapy, whereas patients with more diabetes complications and poorer glycemic control were more likely to be prescribed oral combination therapy or insulin (monotherapy or combination therapy). In conclusion, the study results appear to suggest that the prescribing patterns of Italian GPs and the predictors of different antihyperglycemic drug use are consistent with recent scientific evidence.     

Healthcare costs and prescription adherence with introduction of thiazolidinedione therapy in Medicaid type 2 diabetic patients: a retrospective data analysis

OBJECTIVES: Outcomes in patients with type 2 diabetes may vary depending on the antidiabetic medication used. Observational studies of outcomes of diabetes pharmacotherapy are needed to understand the implications of choice of controller in different populations. This study compared differences in total health care costs, medication adherence, and persistence in patients with type 2 diabetes enrolled in the North Carolina Medicaid Program that were newly started on thiazolidinedione (TZD) therapy with patients starting other oral antidiabetics during the same period. In addition differences among the TZDs with respect to these outcomes were examined. METHODS: A total of 1774 patients newly starting TZD therapy between July 2001 and June 2002 were compared to 1709 patients starting other oral antidiabetic medication (metformin or sulfonylureas) for health care costs and outcomes in the post-medication start year. In addition, a sub-group analysis of health care costs in patients starting either TZD (pioglitazone [n = 1086] versus rosiglitazone [N = 688]) was compared. All included patients had complete enrollment for the 24 months of follow-up. Multivariate techniques incorporating health care utilization in the year prior to start of new therapy were utilized to determine the cost impact of one therapy versus another. RESULTS: Results of multiple regression analyses suggest that patients starting TZD have better treatment adherence and persistence in the post-medication start year compared to patients starting other oral antidiabetics (13% increase in Medication Possession Ratios, and 10% increase in therapy persistence index, both p < 0.001). In addition, patients starting TZDs had 16.1% lower total annual health care costs (p < 0.01) compared to patients starting other oral antidiabetics. There were no differences in adherence and cost outcomes between the 2 TZDs. CONCLUSIONS: Introduction of thiazolidinedione therapy in a Medicaid-enrolled type 2 diabetic population was associated with significantly improved treatment adherence, persistence, and lower annual health care costs in the post-start year compared to patients starting other oral antidiabetics.     

Outcomes associated with introduction of thiazolidinedione therapy in Medicaid enrolled patients with type 2 diabetes: an updated and expanded retrospective analysis

OBJECTIVES: In an earlier analysis, differences in health-care costs, medication adherence, and persistence were examined between patients with type 2 diabetes, enrolled in the North Carolina Medicaid, who had newly started thiazolidinedione (TZD) therapy and those starting other oral antidiabetic agents. In this analysis, the size of the cohort was increased by including 18 months of additional Medicaid data (until December 2004) and sought to: (1) replicate the results of the original study in a larger cohort; and (2) extend the original analysis by providing an additional 18 months of observational follow-up. METHODS: A total of 2660 patients newly starting TZD therapy between July 2001 and December 2003 were compared to 2050 patients starting other oral antidiabetic medication for health-care costs and outcomes in the post-medication start year. In addition, the initial cohort was followed for an additional 18 months to examine if there were any differences in outcomes, such as hospitalization and total health-care costs, that could be associated with the type of therapy. Multivariate regression techniques, incorporating health-care utilization in the year prior to start of new therapy, were used to determine the net cost impact of one therapy versus the other. RESULTS: Multiple regression analyses found that patients starting TZD have better treatment persistence in the post-medication start year compared to patients starting other oral antidiabetic agents (4% increase in therapy persistence index, p < 0.001). In addition, patients starting TZDs had 18.9% lower total annual health-care costs (p < 0.01) compared to patients starting other oral antidiabetic agents. Examination of the original cohort of 3191 patients, for up to an additional 18 months, showed TZD's association with improved adherence rates but not with persistence. Importantly, treatment adherence remained the strongest independent predictor of decreased hospitalization risk and health-care cost reduction in this population. CONCLUSIONS: Introduction of thiazolidinedione therapy in a Medicaid-enrolled type 2 diabetic population was associated with significantly greater treatment adherence, in the post-start year, compared to patients starting other oral antidiabetic agents.     

Economic model of first-line drug strategies to achieve recommended glycaemic control in newly diagnosed type 2 diabetes mellitus

OBJECTIVE: To assess the short-term direct medical costs and effectiveness associated with achieving recommended glycaemic goals using commonly prescribed first-line oral antihyperglycaemic medications in type 2 diabetes mellitus. MATERIALS AND METHODS: A literature-based, decision-tree model was developed to project the number of patients achieving glycosylated haemoglobin values of <7% on oral therapies and the associated costs over a 3-year timeframe. For each first-line strategy, patients could progress to combination therapy using two or more agents prior to the introduction of insulin. The overall cost of treatment included costs (2001/2002 values; US dollars) of comprehensive medical care, laboratory tests, patient education, drug therapy, home glucose monitoring and adverse events. RESULTS: At 3 years, the overall cost of treatment for the various first-line strategies was 6,106 US dollars for glipizide gastrointestinal therapeutic system, 6,727 US dollars for metformin immediate release, 6,826 US dollars for metformin extended release, 7,141 US dollars for glibenclamide (glyburide)/metformin, 7,759 US dollars for rosiglitazone and 9,298 US dollars for repaglinide. Costs of comprehensive routine medical care ranged from approximately 1,538-2,128 US dollars in year 1 and from approximately 952-1,543 US dollars in subsequent years, for controlled and uncontrolled patients, respectively. Adverse events represented <1%, and drug therapies represented approximately 50%, of the overall cost, respectively. Substantial cost differences between the strategies were seen within the first year. Regardless of first-line therapy, patients progressed quickly to combination therapies, with effectiveness among the agents being similar. CONCLUSIONS: Short-term costs required to provide comprehensive diabetes care and achieve glycemic goals can be substantial. The model suggests a sulphonylurea strategy may provide similar effectiveness with cost savings over other agents and should be considered when selecting an initial drug therapy in newly diagnosed patients with type 2 diabetes mellitus.     

Troglitazone: a review of its use in the management of type 2 diabetes mellitus

Troglitazone is the first of a new group of oral antidiabetic drugs, the thiazolidinediones, and is indicated for the treatment of patients with type 2 (non-insulin-dependent) diabetes mellitus. Troglitazone acts by enhancing the effects of insulin at peripheral target sites and, unlike the sulphonylurea drugs, is not associated with hypoglycaemia when administered as monotherapy. Clinical trials with troglitazone (usually 200 to 600 mg/day) in patients with type 2 diabetes mellitus consistently showed marked improvement in glycaemic control, as well as reductions in fasting serum insulin, C-peptide and triglyceride levels. Comparative studies with either glibenclamide (glyburide) or metformin indicated similar glycaemic control with troglitazone or these agents. Serum insulin levels were lower with troglitazone than with glibenclamide. Clinical trials of up to approximately 2 years' duration showed that glycaemic control is maintained with troglitazone on a long term basis. In general, troglitazone is well tolerated by the majority of patients. However, discontinuation of troglitazone because of elevated liver enzyme levels occurs in approximately 2% of patients receiving the drug, and frequent monitoring of liver enzymes is required (e.g. at least 11 times during the first year of therapy). Among patients who started troglitazone therapy in 1998 (after the incorporation of a boxed warning and increased monitoring requirements in the product labelling), the estimated risk of liver-related death is approximately 1 in 100,000. CONCLUSIONS: Troglitazone improves the ability of target cells to respond to insulin. The drug has been shown to improve glycaemic control in patients with type 2 diabetes mellitus when used as monotherapy or in combination with other oral antidiabetic drugs or insulin, and its efficacy is similar to that of glibenclamide or metformin. Although troglitazone is generally well tolerated, close monitoring of liver enzyme function is required to minimise the rare occurrence of serious hepatic dysfunction. Drug acquisition and liver function monitoring costs, as well as potential adverse effects, are important factors that may ultimately determine the precise place of troglitazone in the management of type 2 diabetes mellitus. Nevertheless, as the first member of a new class of oral antidiabetic agents, the thiazolidinediones, troglitazone offers an effective treatment option in patients with type 2 diabetes mellitus through its action of improving insulin sensitivity.     

Cost effectiveness of combination therapy with pioglitazone for type 2 diabetes mellitus from a german statutory healthcare perspective

BACKGROUND: Pioglitazone has been approved in Europe for oral combination therapy for type 2 diabetes mellitus. Along with other agents of the thiazolidinedione class, it has a novel intracellular mechanism of action. Clinical trials with pioglitazone have confirmed a strong product profile in terms of control of blood glucose and lipids. However, the drug acquisition cost for pioglitazone is greater than standard medications for type 2 diabetes. Long-term data regarding the cost effectiveness of pioglitazone-based combination therapy are not available. OBJECTIVE: To evaluate, using a decision analysis model, the cost effectiveness of pioglitazone-based combination therapy compared with relevant alternative medications for the treatment of type 2 diabetes in Germany. METHODS: This study compared the clinical effects and costs of pioglitazone 30 mg added to metformin in patients who failed metformin monotherapy and pioglitazone added to a sulphonylurea in patients who failed sulphonylurea monotherapy, with the most relevant treatment alternatives. A published and validated Markov model was adapted to reflect the management of type 2 diabetes. This simulated the number of severe complications occurring and the mean life expectancy of a diabetic cohort, which was based on the overweight group of the UK Prospective Diabetes Study at year 6 of follow-up. Drug treatment costs, other costs for general management of type 2 diabetes and the costs of complications were combined to compute overall lifetime treatment costs from the perspective of the German statutory healthcare system in 2002. RESULTS: Combination therapy with pioglitazone/metformin was associated with a higher life expectancy (15.2 years) relative to sulphonylurea/metformin (14.9 years) or acarbose/metformin (14.7 years). Likewise, pioglitazone/sulphonylurea (15.5 years) was superior to metformin/sulphonylurea (14.9 years) and acarbose/sulphonylurea (14.8 years). Undiscounted incremental cost-effectiveness ratios in comparison to the next best strategy were euro20,002 per life-year gained (LYG) for pioglitazone/metformin versus sulphonylurea/metformin, and euro8707 per LYG for pioglitazone/sulphonylurea versus metformin/sulphonylurea. After discounting costs and life expectancy at 5% per year, the incremental cost-effectiveness ratio was euro47 636 per LYG for pioglitazone/metformin versus sulphonylurea/metformin, and euro19 745 per LYG for pioglitazone/sulphonylurea versus metformin/sulphonylurea. CONCLUSIONS: In this model, with its underlying assumptions and data, combination therapy with pioglitazone increased life expectancy in overweight type 2 diabetes patients at acceptable cost compared with other well established medications in Germany. These findings should be re-evaluated as soon as additional evidence becomes available from the currently ongoing long-term clinical and economic studies.     

Outcomes associated with introduction of thiazolidinedione therapy in Medicaid enrolled patients with type 2 diabetes: an updated and expanded retrospective analysis

ABSTRACT

Objectives: In an earlier analysis, differences in healthcare costs, medication adherence, and persistence were examined between patients with type 2 diabetes, enrolled in the North Carolina Medicaid, who had newly started thiazolidinedione (TZD) therapy and those starting other oral antidiabetic agents. In this analysis, the size of the cohort was increased by including 18 months of additional Medicaid data (until December 2004) and sought to: (1) replicate the results of the original study in a larger cohort; and (2) extend the original analysis by providing an additional 18 months of observational follow-up.

Methods: A total of 2660 patients newly starting TZD therapy between July 2001 and December 2003 were compared to 2050 patients starting other oral antidiabetic medication for health-care costs and outcomes in the post-medication start year. In addition, the initial cohort was followed for an additional 18 months to examine if there were any differences in outcomes, such as hospitalization and total health-care costs, that could be associated with the type of therapy. Multivariate regression techniques, incorporating health-care utilization in the year prior to start of new therapy, were used to determine the net cost impact of one therapy versus the other.

Results: Multiple regression analyses found that patients starting TZD have better treatment persistence in the post-medication start year compared to patients starting other oral antidiabetic agents (4% increase in therapy persistence index, p < 0.001). In addition, patients starting TZDs had 18.9% lower total annual health-care costs (?p < 0.01) compared to patients starting other oral antidiabetic agents.

Examination of the original cohort of 3191 patients, for up to an additional 18 months, showed TZD's association with improved adherence rates but not with persistence. Importantly, treatment adherence remained the strongest independent predictor of decreased hospitalization risk and health-care cost reduction in this population.

Conclusions: Introduction of thiazolidinedione therapy in a Medicaid-enrolled type 2 diabetic population was associated with significantly greater treatment adherence, in the post-start year, compared to patients starting other oral antidiabetic agents.     

The incremental costs of recommended therapy versus real world therapy in type 2 diabetes patients

ABSTRACT

Background: The goals of diabetes management have evolved over the past decade to become the attainment of near-normal glucose and cardiovascular risk factor levels. Improved metabolic control is achieved through optimized medication regimens, but costs specifically associated with such optimization have not been examined.

Objective: To estimate the incremental medication cost of providing optimal therapy to reach recommended goals versus actual therapy in patients with type 2 diabetes.

Methods: We randomly selected the charts of 601 type 2 diabetes patients receiving care from the outpatient clinics of Massachusetts General Hospital March 1, 1996–August 31, 1997 and abstracted clinical and medication data. We applied treatment algorithms based on 2004 clinical practice guidelines for hyperglycemia, hyperlipidemia, and hypertension to patients’ current medication therapy to determine how current medication regimens could be improved to attain recommended treatment goals. Four clinicians and three pharmacists independently applied the algorithms and reached consensus on recommended therapies. Mean incremental medication costs, the cost differences between current and recommended therapies, per patient (expressed in 2004 dollars) were calculated with 95% bootstrap confidence intervals (CIs).

Results: Mean patient age was 65 years old, mean duration of diabetes was 7.7 years, 32% had ideal glucose control, 25% had ideal systolic blood pressure, and 24% had ideal low-density lipoprotein cholesterol. Care for these diabetes patients was similar to that observed in recent national studies. If treatment algorithm recommendations were applied, the average annual medication cost/patient would increase from $1525 to $2164. Annual incremental costs/patient increased by $168 (95% CI $133–$206) for antihyperglycemic medications, $75 ($57–$93) for antihypertensive medications, $392 ($354–$434) for antihyperlipidemic medications, and $3 ($3–$4) for aspirin prophylaxis. Yearly incremental cost of recommended laboratory testing ranged from $77–$189/patient.

Limitations: Although baseline data come from the clinics of a single academic institution, collected in 1997, the care of these diabetes patients was remarkably similar to care recently observed nationally. In addition, the data are dependent on the medical record and may not accurately reflect patients’ actual experiences.

Conclusion: Average yearly incremental cost of optimizing drug regimens to achieve recommended treatment goals for type 2 diabetes was approximately $600/patient. These results provide valuable input for assessing the cost-effectiveness of improving comprehensive diabetes care.     

Off-label use of exenatide for the management of insulin-resistant type 1 diabetes mellitus in an obese patient with human immunodeficiency virus infection

Exenatide is an incretin mimetic indicated for the treatment of type 2 diabetes mellitus in combination with a sulfonylurea, a thiazolidinedione, metformin, or metformin plus a sulfonylurea or thiazolidinedione. Exenatide lowers postprandial blood glucose levels by stimulating glucose-dependent insulin secretion, inhibiting glucagon secretion, slowing gastric emptying, and increasing satiety. Therapy with exenatide often results in weight loss, which further assists in decreasing insulin resistance. This feature makes the drug an attractive therapeutic option for obese patients. We report the successful off-label use of exenatide in an obese, 40-year-old man with type 1 diabetes and human immunodeficiency virus (HIV) infection who had gastrointestinal intolerance to pramlintide. The patient had experienced a dramatic weight gain secondary to his antiretroviral drugs. This weight gain led to insulin resistance and the development of type 2 diabetes; thus he had characteristics of both types 1 and 2 diabetes, or double diabetes. Before the start of exenatide therapy, he weighed 123 kg, had a body mass index of 42.3 kg/m(2), and had a suboptimal hemoglobin A(1c) value of 8.7%. After 11 months of therapy, the patient lost 24 kg (19.5% of his body weight) and achieved a hemoglobin A(1c) value of 7.3%. His basal insulin requirement was reduced by 25%, and his use of short-acting insulin before breakfast and before dinner was discontinued. In addition, the patient's quality of life substantially improved, as he was able to return to work and exercise after being nearly incapacitated by his weight. To our knowledge, this is the first published case report of the use of exenatide in a patient with type 1 diabetes mellitus or human immunodeficiency virus infection. Given this experience, exenatide may prove to be a useful alternative in selected patients with type 1 diabetes.     

Replacing SUs with incretin-based therapies for type 2 diabetes mellitus: challenges and feasibility

Type 2 diabetes mellitus (T2DM) is a progressive disease characterized by insulin resistance, a steady decline in glucose-induced insulin secretion (most likely caused by a progressive decrease in functional beta-cell mass), and inappropriately regulated glucagon secretion; in combination, these effects result in hyperglycemia. In 1958, sulfonylurea (SU) was introduced to the market as one of the first oral treatments for T2DM. Since then, the ability of SU to stimulate the release of insulin from pancreatic beta-cells by the closure of ATP-sensitive K+-channels has been employed as one of the most widespread treatment options for T2DM. However, SUs are associated with weight gain and a risk of hypoglycemia, and the one-track antidiabetic mechanism of SUs often results in patients being treated with additional antidiabetic drugs. In recent studies, SU has proven to be associated with increased beta-cell apoptosis, suggesting that SU may actually accelerate the progressive decrease in beta-cell mass, thereby promoting the need for insulin replacement. In contrast, the newly developed incretin-based therapies for T2DM employ the beta-cell-preserving properties of incretin hormones - glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). More importantly, incretin-based therapies potentiate glucose-stimulated insulin secretion and may restore reduced glucose-induced insulin secretion in T2DM. Furthermore, the insulinotropic effects of GLP-1 and GIP are glucose-dependent, reducing the risk of hypoglycemia. GLP-1 inhibits glucagon secretion and decreases gastrointestinal motility, in turn reducing food intake and body weight. This feature review focuses on the challenges and feasibilities of replacing SU with incretin-based therapy in patients with T2DM.