Continuous glucose monitoring and metrics for clinical trials: an international consensus statement.

Randomised controlled trials and other prospective clinical studies for novel medical interventions in people with diabetes have traditionally reported HbA1c as the measure of average blood glucose levels for the 3 months preceding the HbA1c test date. The use of this measure highlights the long-established correlation between HbA1c and relative risk of diabetes complications; the change in the measure, before and after the therapeutic intervention, is used by regulators for the approval of medications for diabetes. However, with the increasing use of continuous glucose monitoring (CGM) in clinical practice, prospective clinical studies are also increasingly using CGM devices to collect data and evaluate glucose profiles among study participants, complementing HbA1c findings, and further assess the effects of therapeutic interventions on HbA1c. Data is collected by CGM devices at 1-5 min intervals, which obtains data on glycaemic excursions and periods of asymptomatic hypoglycaemia or hyperglycaemia (ie, details of glycaemic control that are not provided by HbA1c concentrations alone that are measured continuously and can be analysed in daily, weekly, or monthly timeframes). These CGM-derived metrics are the subject of standardised, internationally agreed reporting formats and should, therefore, be considered for use in all clinical studies in diabetes. The purpose of this consensus statement is to recommend the ways CGM data might be used in prospective clinical studies, either as a specified study endpoint or as supportive complementary glucose metrics, to provide clinical information that can be considered by investigators, regulators, companies, clinicians, and individuals with diabetes who are stakeholders in trial outcomes. In this consensus statement, we provide recommendations on how to optimise CGM-derived glucose data collection in clinical studies, including the specific glucose metrics and specific glucose metrics that should be evaluated. These recommendations have been endorsed by the American Association of Clinical Endocrinologists, the American Diabetes Association, the Association of Diabetes Care and Education Specialists, DiabetesIndia, the European Association for the Study of Diabetes, the International Society for Pediatric and Adolescent Diabetes, the Japanese Diabetes Society, and the Juvenile Diabetes Research Foundation. A standardised approach to CGM data collection and reporting in clinical trials will encourage the use of these metrics and enhance the interpretability of CGM data, which could provide useful information other than HbA1c for informing therapeutic and treatment decisions, particularly related to hypoglycaemia, postprandial hyperglycaemia, and glucose variability.

Comparison of Protocols to Reduce Diabetic Ketoacidosis in Patients With Type 1 Diabetes Prescribed a Sodium-Glucose Cotransporter 2 Inhibitor.

OBJECTIVE | Sodium-glucose cotransporter 2 (SGLT2) inhibitors are approved for type 1 diabetes in Europe and Japan, with off-label use in type 1 diabetes in the United States. Although there were no consistent approaches to risk mitigation in clinical trials of these agents, protocols have been developed to try to reduce the risk of diabetic ketoacidosis (DKA). However, a validated risk mitigation strategy does not exist. We reviewed available DKA risk mitigation protocols to better understand the various strategies currently in use. METHODS | We conducted a search of the published medical literature and other medical information sources, including conference presentations, for protocols. We then categorized the information provided into guidance on patient selection, initiation of SGLT2 inhibitors, ketone monitoring, necessary patient action in the event of ketosis or DKA, and inpatient treatment of ketosis or DKA. RESULTS | Patient selection is generally similar among the protocols, although some require a minimum BMI and insulin dose. All protocols advocate routine measurement of ketones, although some insist on blood ketone tests. Although action steps for ketosis varies, all protocols advocate rapid patient intervention. The importance of evaluating ketones and acid-base balance even in the absence of hyperglycemia is emphasized by all protocols, as is the need to continue administering insulin until ketosis has resolved. CONCLUSION | DKA risk mitigation must be pursued systematically in individuals with type 1 diabetes, although the best strategy remains to be determined. Given the ongoing need for adjunctive therapies in type 1 diabetes and current use of SGLT2 inhibitors for this purpose, additional education and research are crucial, especially in the hospital environment, where DKA may not be diagnosed promptly and treated appropriately.

Renal Evaluation and Protection.

Diabetes and diabetic nephropathy have become more prevalent in the elderly population. Diabetic nephropathy has become increasingly prevalent in the elderly population. The presence of this disease in an age group suffering multiple comorbidities has altered the pathophysiology and leading cause of mortality. Mortality has become linked more often to cardiovascular events rather than progression of end-stage-renal-disease, which explains the recent shift of focus of trials to improving cardiovascular-outcomes in patients with diabetes. In this chapter, we emphasize the difference in treatment modalities and goals of therapy in elderly versus young. In addition, we discuss results from recent outcome trials with regards to renal benefits of sodium-glucose co-transporter-2-inhibitors and glucagon-like peptide-1-receptor-agonists.

International Consensus on Risk Management of Diabetic Ketoacidosis in Patients With Type 1 Diabetes Treated With Sodium-Glucose Cotransporter (SGLT) Inhibitors.

Sodium-glucose cotransporter (SGLT) inhibitors are new oral antidiabetes medications shown to effectively reduce glycated hemoglobin (A1C) and glycemic variability, blood pressure, and body weight without intrinsic properties to cause hypoglycemia in people with type 1 diabetes. However, recent studies, particularly in individuals with type 1 diabetes, have demonstrated increases in the absolute risk of diabetic ketoacidosis (DKA). Some cases presented with near-normal blood glucose levels or mild hyperglycemia, complicating the recognition/diagnosis of DKA and potentially delaying treatment. Several SGLT inhibitors are currently under review by the U.S. Food and Drug Administration and European regulatory agencies as adjuncts to insulin therapy in people with type 1 diabetes. Strategies must be developed and disseminated to the medical community to mitigate the associated DKA risk. This Consensus Report reviews current data regarding SGLT inhibitor use and provides recommendations to enhance the safety of SGLT inhibitors in people with type 1 diabetes.

Factors associated with adherence to oral antihyperglycemic monotherapy in patients with type 2 diabetes.

AIM: To estimate the rate of adherence to oral antihyperglycemic monotherapy for patients with type 2 diabetes in the US and describe factors associated with adherence in these patients. MATERIALS AND METHODS: In this retrospective cohort analysis, patients aged 18 years or older with a type 2 diabetes diagnosis received between 1 January 2007 and 31 March 2010 were identified using a large US-based health care claims database. The index date was defined as the date of the first prescription for oral antihyperglycemic monotherapy during this period. Patients had to have continuous enrollment in the claims database for 12 months before and after the index date. Adherence was assessed using proportion of days covered (PDC) and an adjusted logistic regression analysis was performed to evaluate factors associated with adherence (PDC ≥80%). RESULTS: Of the 133,449 eligible patients, the mean age was 61 years and 51% were men. Mean PDC was 75% and the proportion of patients adherent to oral antihyperglycemic monotherapy was 59%. Both mean PDC and PDC ≥80% increased with increasing age and the number of concomitant medications, and were slightly higher in men compared to women. Results from the logistic regression demonstrate an increased likelihood of non-adherence for patients who were younger, new to therapy, on a twice-daily dose, female, or on fewer than three concomitant medications compared to their reference groups. Higher average daily out-of-pocket pharmacy expense was also associated with an increased likelihood of non-adherence. All results were statistically significant (P<0.05). CONCLUSION: Patient characteristics, treatment regimens, and out-of-pocket expenses were associated with adherence to oral antihyperglycemic monotherapy in our study.

A survey of patient preferences for oral antihyperglycemic therapy in patients with type 2 diabetes mellitus.

INTRODUCTION: Previous research has demonstrated a correlation among patient preferences, dosing burden, and medication nonadherence, a well-recognized challenge in type 2 diabetes mellitus (T2DM). The objective of this study was to elicit preferences for alternative dosing regimens for oral antihyperglycemic therapies among patients with T2DM and to quantify differences in dosing preferences among patients with different characteristics. METHODS: Preferences for dosing of oral antihyperglycemic drugs (OAD) were evaluated by surveying patients with T2DM in the United States (US). Survey participants were adult US patients with T2DM who were taking no or only 1 OAD and no injectable therapies. Each patient completed a web-enabled discrete-choice experiment (DCE) including a series of 8 pairs of hypothetical OAD profiles. Each profile was defined by reductions in average glucose, dosing schedule (e.g., once-weekly, once-daily, or twice-daily dosing), chance of mild-to-moderate gastrointestinal side effects, frequency of hypoglycemia, weight change, incremental risk of congestive heart failure, and cost. Each participant also answered a direct question about dosing preference. Random-parameters logit was used to analyze the DCE data. Prespecified subgroups were analyzed. RESULTS: Of 2,262 patients invited to participate, 923 were included in the analysis (mean age 63 years, 45% male, 79% white). Reducing dosing frequency was statistically significantly important to patients; however, it was relatively less important than medication cost or clinical outcomes. On average, patients preferred once-weekly to once-daily dosing. Patients not currently taking an OAD had a stronger preference for once-weekly dosing than patients on treatment (P = 0.012). Patients younger than 45 years had a stronger preference for weekly dosing than older patients (P < 0.075). CONCLUSIONS: For younger patients and patients not currently on treatment, once-weekly dosing may provide additional incentive to initiate and adhere to antihyperglycemic treatment; however, additional research will be required to confirm this hypothesis.

Effect of pill burden on dosing preferences, willingness to pay, and likely adherence among patients with type 2 diabetes.

PURPOSE: To quantify willingness-to-pay (WTP) for reducing pill burden and dosing frequency among patients with type 2 diabetes mellitus (T2DM), and to examine the effect of dosing frequency and pill burden on likely medication adherence. PATIENTS AND METHODS: Participants were US adults with T2DM on oral antihyperglycemic therapy. Each patient completed an online discrete-choice experiment (DCE) with eight choice questions, each including a pair of hypothetical medication profiles. Each profile was defined by reduction in average glucose (AG), daily dosing, chance of mild-to-moderate stomach problems, frequency of hypoglycemia, weight change, incremental risk of congestive heart failure (CHF), and cost. Patients were asked to rate their likely adherence to the profiles presented in each question. Choice questions were based on a predetermined experimental design. Choice data were analyzed using random-parameters logit. Likely treatment adherence was analyzed using a Heckman two-stage model. RESULTS: Of the 1,114 patients who completed the survey, 90 had lower dosing burden (<5 pills/day taken once/day or as needed) for all medications, and 1,024 had higher dosing burden (≥5 pills/day or more than once/day). Reduction in AG was valued most highly by patients. Hypoglycemia, chance of mild-to-moderate stomach problems, weight change, incremental risk of CHF, and daily dosing were less valued. Patients with higher current dosing burden had lower WTP for more convenient dosing schedules than patients with lower current dosing burden. Changes in dosing and cost impacted likely adherence. The magnitude of the impact of dosing on likely adherence was higher for patients with lower current dosing burden than for patients with higher current dosing burden. CONCLUSION: Patients with T2DM were willing to pay for improvements in efficacy, side effects, and dosing. Patients' WTP for more convenient dosing depended on current dosing burden, as did the effect of these attributes on likely adherence.

Factors associated with initiation of antihyperglycaemic medication in UK patients with newly diagnosed type 2 diabetes.

AIM: To assess the factors associated with antihyperglycaemic medication initiation in UK patients with newly diagnosed type 2 diabetes. METHODS: In a retrospective cohort study, patients with newly diagnosed type 2 diabetes were identified during the index period of 2003-2005. Eligible patients were ≥ 30 years old at the date of the first observed diabetes diagnosis (referred to as index date) and had at least 2 years of follow-up medical history (N = 9,158). Initiation of antihyperglycaemic medication (i.e., treatment) was assessed in the 2-year period following the index date. Adjusted Cox regression models were used to examine the association between time to medication initiation and patient age and other factors. RESULTS: Mean (SD) HbA1c at diagnosis was 8.1% (2.3). Overall, 51% of patients initiated antihyperglycaemic medication within 2 years (65%, 55%, 46% and 40% for patients in the 30- < 45, 45- < 65, 65- < 75, 75+ age groups, respectively). Among the treated patients, median (25th, 75th percentile) time to treatment initiation was 63 (8, 257) days. Of the patients with HbA1c ≥ 7.5% at diagnosis, 87% initiated treatment within 2 years. These patients with a higher HbA1c also had shorter time to treatment initiation (adjusted hazard ratio (HR) = 2.44 [95% confidence interval (CI): 1.61, 3.70]; p < 0.0001). Increasing age (in years) was negatively associated with time to treatment initiation (HR = 0.98 [95% CI: 0.97, 0.99]; p < 0.001). Factors significantly associated with shorter time to treatment initiation included female gender and use of cardiovascular medications at baseline or initiated during follow up. CONCLUSIONS: In this UK cohort of patients with newly diagnosed type 2 diabetes, only 51% had antihyperglycaemic medication initiated over a 2-year period following diagnosis. Older patients were significantly less likely to have been prescribed antihyperglycaemic medications. Elevated HbA1c was the strongest factor associated with initiating antihyperglycaemic medication in these patients.

Use of the UKPDS Outcomes Model to predict all-cause mortality in U.S. adults with type 2 diabetes mellitus: comparison of predicted versus observed mortality.

AIMS: The applicability of the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model is unknown in populations with type 2 diabetes mellitus (T2DM) outside the United Kingdom. We compared all-cause mortality predicted from the UKPDS model with observed mortality among T2DM subjects in the U.S. METHODS: we studied participants with T2DM from the National Health and Nutrition Examination Survey 1988-1994 with characteristics comparable to the UKPDS cohort. The 10-year observed all-cause mortality was compared to the UKPDS model-predicted mortality. The Lifetable method was used to estimate the probability of mortality for 10 years following diagnosis. RESULTS: among 156 subjects with characteristics comparable to the UKPDS cohort, mean age was 49.6 years, age at T2DM diagnosis was 47.1 years, and T2DM duration averaged 2.6 years, with follow-up for 10.4 years. The UKPDS model-predicted 10-year mortality was 15.7%, similar to the observed mortality of 14.2%. Corresponding 10-year predicted versus observed mortality was 32.7% versus 32.4% including subjects >age 65, 17.0% versus 19.3% including individuals with pre-existing CVD, and 31.1% versus 20.9% including individuals with diabetes duration ≥ 6 years. CONCLUSION: all-cause mortality predicted by the UKPDS model was comparable to observed mortality in U.S. NHANES participants with characteristics similar to the UKPDS.

Fear of hypoglycaemia: defining a minimum clinically important difference in patients with type 2 diabetes.

BACKGROUND: To explore the concept of the Minimum Clinically Important Difference (MID) of the Worry Scale of the Hypoglycaemia Fear Survey (HFS-II) and to quantify the clinical importance of different types of patient-reported hypoglycaemia. METHODS: An observational study was conducted in Germany with 392 patients with type 2 diabetes mellitus treated with combinations of oral anti-hyperglycaemic agents. Patients completed the HFS-II, the Treatment Satisfaction Questionnaire for Medication (TSQM), and reported on severity of hypoglycaemia. Distribution- and anchor-based methods were used to determine MID. In turn, MID was used to determine if hypoglycaemia with or without need for assistance was clinically meaningful compared to having had no hypoglycaemia. RESULTS: 112 patients (28.6%) reported hypoglycaemic episodes, with 15 patients (3.8%) reporting episodes that required assistance from others. Distribution- and anchor-based methods resulted in MID between 2.0 and 5.8 and 3.6 and 3.9 for the HFS-II, respectively. Patients who reported hypoglycaemia with (21.6) and without (12.1) need for assistance scored higher on the HFS-II (range 0 to 72) than patients who did not report hypoglycaemia (6.0). CONCLUSION: We provide MID for HFS-II. Our findings indicate that the differences between having reported no hypoglycaemia, hypoglycaemia without need for assistance, and hypoglycaemia with need for assistance appear to be clinically important in patients with type 2 diabetes mellitus treated with oral anti-hyperglycaemic agents.

Economic and clinical impact of inpatient diabetic hypoglycemia.

OBJECTIVE: To assess the clinical and economic impact of hypoglycemia that develops during hospitalization of patients with diabetes. METHODS: In this retrospective cohort study, data from 70 hospitals were used to identify the first inpatient encounter for adult patients with diabetes. Patients were included if all blood glucose measurements were 70 mg/dL or higher during the first 24 hours and their primary discharge diagnosis was for a condition other than hypoglycemia. Those who developed laboratory evidence of hypoglycemia (blood glucose <70 mg/dL after 24 hours) were compared with patients whose blood glucose values were all 70 mg/dL or higher. An alternative definition of hypoglycemia (blood glucose <50 mg/dL after 24 hours) was also evaluated. We adjusted for potential confounders with multivariate models. RESULTS: Hypoglycemia had an adverse effect on all outcomes among more than 100,000 diabetic patients. After adjustment, patients with diabetes who developed hypoglycemia had higher charges (38.9%), longer lengths of stay (3.0 days), higher mortality (odds ratio, 1.07; 95% confidence interval, 1.02-1.11), and higher odds of being discharged to a skilled nursing facility (odds ratio, 1.58; 95% confidence interval, 1.48-1.69) than diabetic patients without hypoglycemia (P<.01 for all). In all cases, using the lower threshold (<50 mg/dL) to define hypoglycemia resulted in similar findings with a larger magnitude of differences. CONCLUSIONS: Although a direct causal relationship cannot be inferred, these study findings suggest the importance of carefully maintaining euglycemia during hospitalizations. Whether the observed worse outcomes were due to hypoglycemia itself or whether they were a marker of worse outcomes due to other causes requires further research.

Validity of the adherence estimator in the prediction of 9-month persistence with medications prescribed for chronic diseases: a prospective analysis of data from pharmacy claims.

OBJECTIVE: The aim of this article was to assess the predictive validity of the Adherence Estimator--a 3-item instrument designed to estimate a patient's propensity to adhere to medications prescribed for chronic disease. METHODS: The Adherence Estimator was a 3-item part of a larger survey mailed to adults aged >or=40 years who had a qualifying index prescription filled in June 2008. A qualifying prescription was defined as one for a medication indicated for the treatment of 1 of 5 chronic diseases (cardiovascular disease, dyslipidemia [lipid-lowering drugs], diabetes [oral antihyperglycemics], osteoporosis [oral bisphosphonates], or asthma). Outcomes were compared between the adherence risk groups derived from the Adherence Estimator (low risk = score of 0, medium risk = score of 2-7, and high risk = score of 8-36). Treatment persistence over a period of 9 months was measured using pharmacy claims data. The primary outcome was the median proportion of days covered (PDC) by >or=1 medication during the first 9 months after the index fill. Secondary outcomes included adherence to the index medication, defined as PDC dichotomized to >or=0.80 or <0.80; rate of obtaining a second fill within 30 days of the index fill; and medication possession ratio (MPR) for refill adherence. RESULTS: There were 1676 usable responses. Ages ranged from 40 to 88 years, with a mean of 64.6 years. Almost two thirds (1076/1676 [64.2%]) of the sample were female, and 1483/1676 (88.5%) were white. Statistically significant associations for all 3 pairwise comparisons (low vs medium risk, low vs high risk, and medium vs high risk) were observed between the Adherence Estimator risk groups for: (1) median PDC (0.655, 0.598, and 0.484 in the low-, medium-, and high-risk groups, respectively [all, false discovery rate [FDR] <0.05]); (2) PDC categorized (293/711 [41.21%], 200/588 [34.01%], and 105/377 [27.85%] [all, FDR <0.05]); and (3) rate of obtaining a second fill for the index medication within 30 days (489/711 [68.78%], 374/588 [63.61%], and 207/377 [54.91%] [all, FDR <0.05]). The low- and high-risk groups differed from one another on: (1) persistence with the index medication at 9 months (265/711 [37.27%] and 95/377 [25.20%]); (2) persistence with >1 medication at 9 months (291/711 [40.93%] and 108/377 [28.65%]); and (3) obtaining a second fill for any medication within 30 days (501/711 [70.46%] and 219/377 [59.09%]) (all, P < 0.05). The low- and high-risk groups differed significantly from one another in MPR for refill adherence (0.912 vs 0.866). Results observed within diseases mirrored those for the total sample, but with less precision. CONCLUSION: In the present analysis of the validity of the Adherence Estimator in predicting adherence, baseline propensity to adhere to medications prescribed for chronic diseases was statistically associated with several measures of adherence and persistence, as derived from pharmacy claims data, over a 9-month period.

Treatment with sitagliptin or metformin does not increase body weight despite predicted reductions in urinary glucose excretion.

BACKGROUND: We used a mathematical model to estimate the contribution of urinary glucose excretion (UGE) to reported changes in body weight (BW) following oral antihyperglycemic agent (AHA) therapy. This modeling approach was used to gain novel insight into the mechanisms by which oral AHA affects BW. METHODS: Twenty-four hour glucose profiles were used to predict UGE before and after treatment with oral AHA. Model-predicted changes in BW due to reduced UGE were compared with reported changes in BW to quantify non-UGE-dependent effects (fluid retention, food intake, and energy expenditure). RESULTS: In type 2 diabetes patients [hemoglobin A1c (HbA1c) >7.3%], the energy lost to UGE is predicted to decrease an average of 100 kcal/day for each 1% decrease in HbA1c. This effect, alone, is predicted to increase BW 1.4 kg after 6 months. Differences from this value reported for changes in BW with oral AHA therapy (+1.4 kg for pioglitazone and rosiglitazone; -0.4 kg for glyburide; -0.9 kg for sitagliptin and vildagliptin; -2.3 kg for metformin) are therefore predicted to be due to additional, non-UGE-dependent mechanisms. CONCLUSIONS: Weight gain following thiazolidinedione therapy is predicted to result from both reduced UGE and non-UGE-dependent mechanisms. Reduced UGE alone is predicted to account for most of the weight gain reported following sulfonylurea therapy. Weight loss observed in response to metformin and weight maintenance observed in response to dipeptidyl peptidase-4 inhibitors may result from an increase in satiety, energy expenditure, or both.

Contemporary analysis of secondary failure of successful sulfonylurea therapy.

OBJECTIVE: To revise older estimates of secondary failure that may no longer describe the contemporary pattern of sulfonylurea (SU) monotherapy and to identify predictors of such failure. METHODS: We identified 4,091 patients who achieved hemoglobin A1c (A1C) <8% within 1 year after initiation of SU therapy as their first-ever antihyperglycemic drug after January 1, 1996. The study subjects underwent follow-up until they added or switched antihyperglycemic medication, had A1C > or =8%, or terminated health plan membership or until December 31, 2004. We defined secondary failure by using two separate but overlapping approaches: (1) the addition of or switch to another antihyperglycemic drug after 6 months of SU therapy or (2) the first A1C measurement > or =8.0%. RESULTS: The level of A1C achieved within 1 year after initiation of SU treatment was the most powerful predictor of secondary SU failure. About 50% of patients whose best A1C was 7.0% to 7.9% added or switched antihyperglycemic drugs within 40 months, whereas it took nearly 60 months for those in the 6.0% to 6.9% A1C category and 74 months in the A1C <6.0% category to reach a 50% failure rate. Similarly, more than half of those patients whose best A1C was 7.0% to 7.9% had an A1C value > or =8% within 24 months, whereas it took nearly 60 months for study subjects in the 6.0% to 6.9% A1C category and 86 months for those in the <6.0% category to have SU failure. Younger age and weight gain were also predictive of failure. CONCLUSION: Secondary failure of SU therapy is inversely associated with the level of A1C achieved within the first year of SU monotherapy. Clinicians should quickly consider therapeutic adjustments to lower the A1C level rapidly if initial success is not achieved.

Reassessment of cardiovascular risk in diabetes.

PURPOSE OF REVIEW: To review recent trials and reassess cardiovascular risk in people with diabetes. RECENT FINDINGS: Recent clinical trials have tended to focus on lower-risk participants with diabetes who have had event rates considerably lower than participants in the early lipid trials. Statin studies have generally shown benefit in those without cardiovascular disease and at lower levels of low-density lipoprotein cholesterol. Results of fibrate and glitazone studies have been mixed; the question of benefit among statin-treated patients remains unanswered. Investigators failed to confirm the benefits of glucose control observed in the original Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction study possibly due to study design issues. Epidemiologic follow-up of the Diabetes Control and Complications Trial showed sustained benefit of glucose control. A number of studies have shown the benefit of inpatient control of blood glucose. We await the results of ongoing blood pressure trials and other ongoing trials, which should provide much new information. A conceptual model of cardiovascular risk for people with diabetes mellitus based on the UK Prospective Diabetes Study outcomes model is discussed. SUMMARY: The majority of adults with diabetes have a substantially greater risk compared with those without diabetes and a small percentage has very high risk. A minority of individuals may have considerably lower 10-year risk.

Trends in lipid management among patients with diabetes.

OBJECTIVE: To examine trends in lipid management (cholesterol testing, treatment, and goal attainment) among patients with diabetes and to analyze the factors associated with initiation of lipid-lowering therapy. METHODS: We conducted a longitudinal, retrospective study of patients with diabetes identified during a 24-month baseline period (January 1, 1995, to December 31, 1996) and for whom follow-up was continued for 5 years (1997 to 2001). Generalized estimating equations were used to test for time trend effects in lipid management. We modeled the days from baseline to the first lipid-lowering prescription fill date with a multivariate Cox proportional hazards regression model. RESULTS: Rates of lipid testing, treatment, and goal attainment significantly improved (P<0.001) during the 5-year study period: from 37% to 67% for lipid testing; from 19% to 41% for treatment with a lipid-lowering agent; from 22% to 37% for achievement of low-density lipoprotein cholesterol (LDL-C) levels < 100 mg/dL; and from 54% to 75% for achievement of LDL-C levels < 130 mg/dL. The relative likelihood (hazard rate) of treatment with lipid-lowering agents was greater for patients with LDL-C levels > or = 100 mg/dL relative to patients with LDL-C concentrations < 100 mg/dL. Treatment with lipid-lowering agents of patients with a cardiovascular event during follow-up was approximately 3 times more likely relative to those without such an event. CONCLUSION: We found that rates of lipid testing, treatment, and goal attainment improved significantly between 1997 and 2001. Nevertheless, ample room for improvement of these rates continues to exist. Particular attention may be warranted to ensure that patients with diabetes receive lipid-lowering agents not only after a cardiovascular event but also before such an event occurs.

The impact of losartan on the lifetime incidence of end-stage renal disease and costs in patients with type 2 diabetes and nephropathy.

INTRODUCTION: The RENAAL (Reduction of Endpoints in Non-insulin dependent diabetes with the Angiotensin II Antagonist Losartan) study demonstrated that, in hypertensive patients with type 2 diabetes mellitus and nephropathy, treatment with losartan plus conventional antihypertensive therapy (CT) reduced the relative risk of end-stage renal disease (ESRD) by 29% versus placebo over the time span of the study (mean patient follow-up of 3.4 years). The objective of this study was to project the effect of losartan compared with placebo on the lifetime incidence of ESRD and associated costs (from a US healthcare system perspective). METHODS: To estimate lifetime incidence of ESRD, we used a competing risks method to account for the risk of death without ESRD. We estimated the cost (US dollars, year 2002 values) associated with ESRD by combining the cumulative incidence of ESRD with the lifetime cost associated with ESRD. Total cost was estimated as the sum of the cost associated with ESRD, the cost of losartan study therapy and other costs (non-ESRD/non-losartan) expected for patients with type 2 diabetes. Survival was estimated by weighting the life expectancies with and without ESRD by the cumulative risk of ESRD. Costs and outcomes were discounted by 3% per annum. RESULTS: We projected a lower lifetime incidence of ESRD for losartan patients (66%) compared with placebo patients (83%). This reduction in ESRD resulted in a decrease in cost associated with ESRD of US dollars 31,803 per patient and a gain of 0.99 life-years per patient (0.70 discounted). After accounting for the cost of losartan and the additional cost associated with greater survival, we projected that treatment with losartan would result in a lifetime net saving of US dollars 24,632 per patient. CONCLUSION: Treatment with losartan plus CT in patients with type 2 diabetes and nephropathy reduced the within-trial incidence of ESRD and is projected to result in lifetime reductions in ESRD and associated costs, and increased survival, versus placebo.