Kimberly G. Brodovicz

Glycemic Response and Attainment of A1C Goals Following Newly Initiated Insulin Therapy for Type 2 Diabetes

OBJECTIVE To identify the characteristics associated with glycemic response to newly initiated insulin therapy. RESEARCH DESIGN AND METHODS We identified 1,139 type 2 diabetic patients who initiated insulin therapy between 1 January 2009 and 30 June 2010. Outcomes of interest were the proportion of patients achieving A1C <7% and mean change in A1C within 3–9 months. RESULTS Mean A1C at insulin initiation was 8.2 vs. 9.2% among those who did and did not attain A1C <7% (P < 0.001). Within a mean of 5 months, 464 (40.7%) patients attained A1C <7%. In multivariable analyses controlling for insulin regimen, dose, and oral agent use, preinsulin A1C was responsible for nearly all the explained variance in A1C change. Each one percentage point of preinsulin A1C reduced the probability of attaining <7% by 26% (odds ratio 0.74 [95% CI 0.68–0.80]). CONCLUSIONS Insulin initiation at lower levels of A1C improves goal attainment and independently increases glycemic response.

Incidence and prevalence of diabetic ketoacidosis (DKA) among adults with type 1 diabetes mellitus (T1D): a systematic literature review

Objectives To summarise incidence and prevalence of diabetic ketoacidosis (DKA) in adults with type 1 diabetes (T1D) for the overall patient population and different subgroups (age, sex, geographical region, ethnicity and type of insulin administration). Design Systematic literature review (SLR). Data sources Medline (via PubMed) and Embase (1 January 2000 to 23 June 2016). Study selection Peer-reviewed observational studies with reported data on the incidence or prevalence of DKA in T1D adults were included. A single reviewer completed the study screening and selection process and a second reviewer performed an additional screening of approximately 20% of the publications; two reviewers independently conducted the quality assessment; the results were narratively synthesised. Results Out of 1082 articles, 19 met the inclusion and exclusion criteria, with two additional studies identified that did not specify the patient age range and are therefore not included in the SLR. Overall, eight studies reported incidence with a range of 0–56 per 1000 person-years (PYs), with one outlying study reporting an incidence of 263 per 1000 PYs. Eleven studies reported prevalence with a range of 0–128 per 1000 people. Prevalence of DKA decreased with increasing age. Subgroup analyses were performed using data from no more than two studies per subgroup. There was a higher prevalence of DKA reported in women, non-whites and patients treated with insulin injections compared with men, whites and patients using continuous subcutaneous insulin infusion pumps, respectively. Conclusions To our knowledge, this is the first SLR on the epidemiology of DKA in T1D adults. Despite an increasing prevalence of T1D in recent years, DKA in adults has been poorly characterised. In an era when the benefit–risk profiles of new antidiabetic therapies are being evaluated, including the potential risk of DKA, there is a clear need to better elucidate the expected rate of DKA among T1D adults.

Claims-based studies of oral glucose-lowering medications can achieve balance in critical clinical variables only observed in electronic health records

To evaluate the extent to which balance in unmeasured characteristics of patients with type 2 diabetes (T2DM) was achieved in claims data, by comparing against more detailed information from linked electronic health records (EHR) data.

Preferential prescribing and utilization trends of diabetes medications among patients with renal impairment: Emerging role of linagliptin and other dipeptidyl peptidase 4 inhibitors

Although many newer diabetes medications have become available in the last decade, most have not been widely studied in populations with chronic kidney disease under routine care. Linagliptin, a recently marketed dipeptidyl peptidase 4 (DPP‐4) inhibitor, is the only agent in the U.S. that does not require dose adjustment in patients with diabetes mellitus type 2 (T2DM) and renal impairment. We sought to describe baseline kidney function and other key characteristics among patients with diabetes mellitus type 2 (T2DM) initiating linagliptin and other diabetes medications, and to explore prescribing patterns among T2DM patients with moderate to severe renal impairment before and after the launch of linagliptin.

Safety of non-insulin glucose-lowering drugs in pregnant women with pre-gestational diabetes: A cohort study

To evaluate the association between use of non‐insulin antidiabetics in early pregnancy and the risk of miscarriages, stillbirths and major structural malformations.

Real world management of pregestational diabetes not achieving glycemic control for many patients in the UK

Our goal was to describe the management of pregestational diabetes in pregnant women in the United Kingdom.

Time between laboratory tests and acute liver and kidney injury diagnosis codes in CPRD: Are we doing it right?

Background: Non-inferiority trials are associated with methodological challenges. The European Medicines Agency (EMA) does not have a guideline on designing non-inferiority trials and recommend to define the non-inferiority margin based on clinical and statistical considerations. However, they do not recommend a specific method to determine the margin. Objectives: To assess the challenges in designing non-inferiority trials for drugs intended to be marketed in Europe. Methods: Using the database of the Dutch Medicines Evaluation Board (MEB), a search in recent (2014 and 2015) final EMA scientific advice letters was conducted to identify design proposals that were sent by pharmaceutical companies to the EMA about non-inferiority trials. Each scientific letter is for one drug, and it includes proposals for different aspects of the trial with a response from the EMA to each proposal. The proportion of the accepted proposals by the EMA was assessed taking into account the therapeutic class and the type of the drug application (orphan vs other drugs) using generalized estimating equations with an exchangeable correlation matrix to account for clustering of proposals within letters. Results: The EMA accepted 142 of 232 (61%) of the total proposals. Almost 65% of the proposals were for three therapeutic classes: anti-infectives (most common), drugs for endocrine disorders (mainly anti-diabetics), and oncology drugs. The EMA acceptance did not differ between proposals for endocrine drugs vs anti-infectives (OR: 1.30, 95%CI 0.52 to 3.24) and between oncology drugs vs anti-infectives (OR: 0.54, 95%CI 0.12 to 2.47). The EMA acceptance also did not differ between orphan vs other drug applications (OR: 0.47 95%CI 0.19 to 1.14). The non-inferiority margin was the main challenge, only 25 of 61 (41%) proposals for the choice of the margin were accepted. There was no common approach proposed by pharmaceutical companies to define the margin (the recommended approach by the EMA was proposed for only 18 of 61 margins) nor a common method of the recommended approach. Conclusions: There are many questions about the design of non-inferiority trials with the choice of the inferiority margin as the main challenge. We did not find that the challenge was related to one of the three most common therapeutic classes or to a type of drug applications. This study shows that more explicit guidance from the EMA on the rationale for choosing different approaches to define the margin is needed.against myocardial infarction in UK adults aged at least 65y Background A recent investigation using routinely collected health records found the influenza vaccine to be effective against heart failure. However, treatment of overt myocardial infarction (MI) events is important in preventing progression to heart failure, especially in older adults, yet evidence for the association between respiratory disease and subsequent MI is from observational data and subject to confounding bias.Background: Cough and angioedema are well-known adverse effects of angiotensin-converting enzyme (ACE) inhibitors. Some observational studies in patients using ACE inhibitors have observed that women have a higher incidence of cough and angioedema than men. Objectives: To evaluate based on randomized controlled trials (RCTs), whether the risks of developing cough and angioedema with ACE inhibitors are modified by sex. Methods: We searched PubMed and Cochrane databases for all years to August 2016. We included RCTs that contain information about the incidence of cough and angioedema in users of ACE inhibitors and controls (active/placebo) in men and women. We performed meta-analyses using the random effects model. Pooled risk ratios (RRs) for cough and angioedema associated with ACE inhibitors in women and men were estimated and tested for interaction. Results: We included four RCTs in our analysis (three studies for cough and two studies for angioedema). We found that there was no difference in the RR to develop cough or angioedema for ACE inhibitors versus controls between women and men. For cough in women, the RR was 3.70; 95% CI (2.55-5.35) and for men, 2.61; 95% CI (1.30-5.27) (P value for interaction 0.39). For angioedema, these RRs were 5.56; 95% CI (2.45-12.62) and 6.35; 95% CI (1.81-22.36), respectively (P-value for interaction 0.86). Conclusions: Our meta-analyses show that the risks of developing cough and angioedema associated with ACE inhibitors are not modified by sex. However, these findings should be interpreted cautiously due to limited number of studies involved.

Incidence of Chronic Kidney Disease and Progression of Renal Dysfunction in Type 2 Diabetes-The Role of Albuminuria

Chronic kidney disease (CKD) is typically assessed by estimated glomerular filtration rate (eGFR), but the predictive value of albuminuria to worsening eGFR in routine clinical practice has not been well documented. We calculated the rate of progression of renal dysfunction measured by eGFR for clinically recognized categories of albuminuria. Using a longitudinal design and the electronic medical records of Kaiser Permanente Northwest, we identified 13,358 diabetes patients who had a serum creatinine (SCr) and urine albumin creatinine ratio (UACR) in 2006-2012 and at least one subsequent measure of each 2006-2016. From those values, we allocated each patient to a baseline eGFR and UACR category according to Kidney Disease: Improving Global Outcomes guidelines. We then calculated progression rates to each higher category of eGFR per 1,000 person-years (p-y) over 11 years of follow-up adjusted for age, sex, race/ethnicity, systolic blood pressure, and use of angiotensin-converting-enzyme inhibitors (ACEi) or angiotensin II receptor antagonists (ARB). We compared these rates by baseline UACR categories. Higher levels of albuminuria at baseline significantly increased the risk of progression of eGFR-based kidney dysfunction (Table). Our results from routine clinical practice demonstrate the key role of albuminuria in the worsening of renal function in a general diabetes population. Disclosure G. Nichols: Research Support; Self; Boehringer Ingelheim GmbH, Amarin Corporation, Janssen Pharmaceuticals, Inc., Sanofi. A. Deruaz-Luyet: Employee; Self; Boehringer Ingelheim GmbH. S. Hauske: Employee; Self; Boehringer Ingelheim GmbH. K. Brodovicz: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc..

Prevalence and incidence of urinary tract and genital infections among patients with and without type 2 diabetes

OBJECTIVE Epidemiological data on genitourinary infections (GUIs) comparing patients with and without type 2 diabetes (T2DM) is scant. We aimed to estimate the incidence of urinary tract infections (UTIs), genital infections (GIs), or any GUI in total and stratified by history of GUI and sex. RESEARCH DESIGN AND METHODS We identified 39,295 patients in the Kaiser Permanente Northwest health plan with T2DM and an equal number of age and sex matched patients without diabetes. The cohort was followed for up to 9years (2006-2014). We calculated incidence rates and corresponding 95% confidence intervals (CI) of any GUI, UTIs and GIs adjusting for age, sex, race, BMI, presence of chronic kidney disease, annual number of outpatient visits, and diuretic use. RESULTS Adjusted incidence of any GUI was 97.2/1000person-years (p-y) (95% CI 95.5-98.8) among the T2DM cohort vs. 79.7/1000 p-y (78.3-81.2) among those without diabetes. T2DM was associated with an adjusted 25% increased risk of UTI (rate ratio 1.25, 95% CI 1.22-1.29), a 26% increased risk of GI (1.26, 1.22-1.31) and a 22% increased risk of any GUI (1.22, 1.19-1.25). Incidence rates were lower among those with no GUI history, but the relative risks were similar. Women in both groups had higher incidence rates of GUIs than men. CONCLUSIONS T2DM was associated with increased risks of any GUI, UTIs and GIs. Incidence rates of UTIs were higher than rates of GIs, but the relative risk of GIs was essentially identical. A similar pattern was observed when stratifying by sex. SIGNIFICANCE OF THE STUDY RESEARCH QUESTIONS.