Current Diabetes Medications Research Articles

Socio-Demographic and Clinical Factors Associated with Poor Glycemic Control Among Patients of Type-2 Diabetes Mellitus Presenting at a Tertiary Healthcare Facility

Objective: To identify socio-demographic and clinical factors associated with poor glycemic control in type-2 diabetes mellitus patients at a tertiary healthcare facility. Methodology: This cross-sectional study was conducted at Outpatient department of Medicine, Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from February 2022 to July 2022, included 246 known type-2 diabetes patients of both genders, aged 18 to 75, with at least three consecutive days of fasting blood glucose (FBG) measurements. We assessed socio-demographic and clinical characteristics and classified glycemic control according to ADA guidelines: FBG between 80-130 mg/dl as good control and FBG above 130 mg/dl as poor control. We recorded the prevalence of good and poor glycemic control and compared them based on various socio-demographic and clinical factors. Results: Among 246 patients, 152 (61.8%) were male, with a mean age of 46.47±11.55 years and a mean BMI of 23.13±5.01 kg/m². The mean diabetes duration was 9.18±7.50 years, and 132 (53.7%) patients had a disease duration > 5 years. Diabetes-related complications were present in 156 (63.4%) patients. Poor glycemic control was found in 137 (55.7%) patients. Significant associations with poor glycemic control were observed for age (p<0.001), educational status (p<0.001), BMI (p=0.002), residential status (p=0.013), family history of diabetes (p<0.001), diabetes duration (p<0.001), and current diabetes medications (p=0.001). Conclusion: A majority (55.7%) of type-2 diabetes patients in our study had poor glycemic control. Factors such as increasing age, BMI, education level, residential status, family history of diabetes, longer disease duration, and current diabetes medications were significantly associated with poor glycemic control.

1043-P: Uncovering Root Causes Contributing to Persistent Gaps in Glycemic Control and Effective Weight Management in Patients with Type 2 Diabetes and Obesity

This QI initiative in 2 large US-based community health systems assessed root causes hindering A1C control and weight management in people with T2D and obesity through health care provider (HCP) surveys (n = 29), baseline EMR audits (n = 100), team-based audit-feedback (AF) sessions, and patient-provider collaborative education sessions. Lack of treatment access and delayed treatment intensification were identified as factors contributing to inadequate A1C control. In the survey, 48% of HCPs reported providing treatment access support as a top barrier. Missed opportunities to escalate care were revealed through gaps in key care measures for patients not on target to achieve their A1C goal, including reevaluating current diabetes medication (77% HCPs reported routinely performing) and referring patients to a diabetes care and education specialist (49%). Following the AF intervention, the percentage of HCPs who plan to consider therapy escalation within 3 months increased from 38% to 80%. Following collaborative education, the percentage of patients who reported understanding the importance of achieving their A1C goal increased from 47% to 71% and 81% committed to taking a more active role in their diabetes management and self-care. Gaps were uncovered in weight management counseling, support, and shared decision-making (SDM). Asking patients about treatment goals was documented in 57% of charts. Reporting weight loss goal discussion every 3 months were 60% of HCPs and 33% of patients. Following AF sessions, the percentage of HCPs who plan to prioritize SDM as a top 2 goal increased from 21% to 53% and HCPs committed to updating patient materials to support more productive conversations about individual health goals. Key factors hindering attainment of A1C and weight management goals revealed through this study include gaps in treatment access, treatment intensification, SDM, and weight management counseling, support. Disclosure E.Zyborowicz: None. C.Heggen: None. M.A.Rodriguez: None. J.D.Carter: None. J.P.Frias: Advisory Panel; Becton, Dickinson and Company, Pfizer Inc., Sanofi, Consultant; Akero Therapeutics, Inc., 89bio, Inc., Aimmune, Boehringer Ingelheim Inc., Eli Lilly and Company, Carmot Therapeutics, Inc., Echosens, Merck & Co., Inc., Metacrine, Inc., Novo Nordisk, Pfizer Inc., Sanofi, Employee; Ionis Pharmaceuticals, Research Support; Akero Therapeutics, Inc., 89bio, Inc., Altimmune, Axcella Health Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Intercept Pharmaceuticals, Inc., Carmot Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Metacrine, Inc., Novo Nordisk, Oramed Pharmaceuticals, Novartis, Pfizer Inc., Sanofi, Speaker's Bureau; Eli Lilly and Company, Sanofi. Funding Eli Lilly and Company (A-31209)

Diabetes and the risk of hospitalisation for infection: the Atherosclerosis Risk in Communities (ARIC) study.

Aims/hypothesisThe aim of this work was to assess the association between diabetes and risk for infection-related hospitalisation and mortality.MethodsWe conducted a prospective cohort analysis of the Atherosclerosis Risk in Communities (ARIC) study. Diabetes was defined as a fasting glucose ≥7 mmol/l or non-fasting glucose ≥11.1 mmol/l, self-report of a diagnosis of diabetes by a physician, or current diabetes medication use. Hospitalisation for infection was ascertained from hospital discharge records. Participants were followed from 1987–1989 to 2019.ResultsWe included 12,379 participants (mean age 54.5 years; 24.7% Black race; 54.3% female sex). During a median follow-up of 23.8 years, there were 4229 new hospitalisations for infection. After adjusting for potential confounders, people with (vs without) diabetes at baseline had a higher risk for hospitalisation for infection (HR 1.67 [95% CI 1.52, 1.83]). Results were generally consistent across infection type but the association was especially pronounced for foot infection (HR 5.99 [95% CI 4.38, 8.19]). Diabetes was more strongly associated with hospitalisation for infection in younger participants and Black people. Overall infection mortality was low (362 deaths due to infection) but the adjusted risk was increased for people with diabetes (HR 1.72 [95% CI 1.28, 2.31]).Conclusions/interpretationDiabetes confers significant risk for infection-related hospitalisation. Enhancing prevention and early treatment of infection in those with diabetes is needed to reduce infection-related morbidity and mortality.Graphical abstract Supplementary Information The online version of this article (10.1007/s00125-021-05522-3) contains peer-reviewed but unedited supplementary material.

Abstract P049: Diabetes And The Risk Of Hospitalization With Infection

Introduction: Mechanistic research suggests that diabetes may increase susceptibility to infection. However, few epidemiologic studies have examined this association. Hypothesis: We hypothesize that adults with diabetes will have a higher risk for infection compared to those without diabetes. Methods: We conducted a prospective cohort analysis of diabetes and incident hospitalization with infection using data from the Atherosclerosis Risk in Communities (ARIC) Study. We used Cox regression models with adjustments for demographics, health behaviors, and cardiometabolic and kidney functioning measures. Diabetes status at baseline (1987-1989) was defined as a fasting glucose ≥126 mg/dL or non-fasting glucose ≥200 mg/dL, or self-report of a diagnosis of diabetes, or current diabetes medication use. First hospitalization with any infection and specific types of infections (respiratory, urinary, foot, sepsis, and postoperative wound) were ascertained from ICD-9 codes in hospital discharge records, with follow-up to September 30, 2015. Results: We included 13,356 participants (mean age, 55; 26% black; 54% female). During a median follow-up of 18.8 years, there were 7,791 incident hospitalizations with infection. Compared to those without diabetes at baseline, those with diabetes had a greater risk for hospitalization with any infection (adjusted HR: 1.55 [95% CI: 1.45-1.66], Table ). Results were generally consistent across infection type, and differences were especially pronounced for foot infections (adjusted HR: 6.35 [95% CI: 5.27-7.64]). Conclusion: The COVID-19 pandemic has heightened interest in the link between diabetes and susceptibility to infection. Our study suggests diabetes confers significant risk for infection. Enhancing diabetes prevention and management may reduce infection-related morbidity and mortality.

Characteristics and Comorbidities at Start of Tuberculosis Treatment in Three Regions of the Philippines: The St-ATT Cohort

Background: Diabetes and undernutrition are common risk factors for tuberculosis (TB), associated with poor treatment outcomes and exacerbated by TB. Here we describe the characteristics and non-communicable multimorbidity (co-occurrence of 2 or more medical conditions) in Filipino adults at the time of initiating a new TB treatment regimen enrolled into the Starting Anti-TB Treatment (St-ATT) Cohort. Methods and Findings: Nine-hundred participants (69.6% male) were enrolled from 13 public health facilities in Metro Manila (N=184), Negros Occidental (N=372) and Cebu (N=344) within 5 days of starting treatment including 133 (14.8%) initiating the 9 month WHO shorter treatment regimen for multi-drug resistant TB (MDR-TB). Diabetes was defined as HbA1c ≥6.5% and/or current diabetes medication; hypertension as systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg and/or current anti-hypertensive medication, anaemia as haemoglobin <11 g/dl and moderate/severe undernutrition as body-mass-index <17 kg/m2. The most common comorbidities were moderate/severe undernutrition 23.4% (210/899), diabetes 22.5% (199/881), hypertension 19.0% (164/864) and moderate/severe anaemia 13.5% (121/899). Fifty-eight percent had ≥1 of these comorbid conditions (496/847), with 17.1% having ≥2; the most common combination being diabetes and hypertension (N=57, 6.7%). Just over half of diabetes (54.8%) and hypertension (54.9%) was previously undiagnosed, and lack of glycemic control (HbA1c<8.0%) was common in those already on medication (N=50/73, 68.5%). MDR-TB treatment was associated with increased odds of diabetes (Adjusted odds ratio (AOR) = 2.48, 95% CI: 1.55-3.95); but decreased odds of hypertension (AOR=0.55, 95% CI: 0.39-0.78). HIV infection was only associated with anaemia (AOR=4.51, 95% CI: 1.01-20.1). Previous TB treatment was associated with moderate/severe undernutrition (AOR = 1.98, 95% CI: 1.40-2.80), as was increased duration of TB-symptoms before starting treatment and household food insecurity. No associations for sex, alcohol or tobacco use were observed. MDR-TB treatment was marginally associated with having ≥2 comorbidities (OR = 1.52, 95% CI: 0.97-2.39). Conclusions: TB treatment programmes need to consider planning for a large proportion of persons requiring diagnosis and management of comorbidities with the potential to adversely affect TB treatment outcomes and quality of life. Of the conditions examined here, dietary advice and nutritional management are considered usual components of comprehensive care.

Abstract 14434: Identification and Predictors for Cardiovascular Disease Risk Equivalents Among Adults With Diabetes Mellitus

Background: It is not well quantified if diabetes mellitus (DM) as a cardiovascular disease (CVD) risk equivalent depends on DM severity and other CVD risk factors. Methods: We pooled 4 US community-based cohorts (ARIC, JHS, MESA, FHS Offspring) and classified subjects by baseline DM/CVD status. DM+/CVD- was further classified by DM duration, HbA1c control or DM medication. Hazard ratios (HR) were estimated for CVD during a median follow-up of 14 years. Subgroup analysis comparing the HR of DM+/CVD- vs. DM-/CVD+ was done by CVD risk factors. We integrated all factors that impacted DM-conferred CVD risk and defined one with DM+/CVD- as CVD risk equivalent when his/her CVD risk was as high or higher than that if he/she had DM-/CVD+. CVD risk profile and event risk were compared between the CVD risk equivalent subgroups in DM+/CVD-. Results: The pooled cohort included 27,732 adults (mean age of 58 years, 45% males). CVD event rates per 1000 P-Y were 16.3, 33.3, 40.9 and 69.0 among those with DM-/CVD-, DM+/CVD-, DM-/CVD+ and DM+/CVD+, respectively. DM participants with HbA1c≥7%, DM duration over 10 years, or DM medication use had similar CVD risk as those with DM-/CVD+ while those without these factors had lower CVD risk; DM+/CVD- had similar CVD risk as those DM-/CVD+ among women, age &lt;55 years, White race, or high triglyceride groups (Figure). Among those with DM+/CVD-, 17.5% were found to be CVD risk equivalents. Compared to those non-CVD risk equivalent DM, they had lower 10-year PCE scores (14.8% vs. 22.7%, p&lt;0.0001) however higher actual CVD event rates (44.9 vs. 31.0 per 1000 P-Y). Conclusion: Among CVD-free adults with DM, fewer than 20% are actually CVD risk equivalents. Poor HbA1c control, long DM duration, and current diabetes medication use were identified as predictors of CVD risk equivalent status and DM was more detrimental for CVD risk if one is female, younger age, White, or with high triglycerides. These risk enhancing factors should be considered in the treatment decision.

Patterns and predictors of co-morbidities in Tuberculosis: A cross-sectional study in the Philippines

Diabetes and undernutrition are common risk factors for TB, associated with poor treatment outcomes and exacerbated by TB. We aimed to assess non-communicable multimorbidity (co-occurrence of two or more medical conditions) in Filipino TB outpatients, focusing on malnutrition and diabetes. In a cross-sectional study, 637 adults (70% male) from clinics in urban Metro Manila (N = 338) and rural Negros Occidental (N = 299) were enrolled. Diabetes was defined as HbA1c of ≥6.5% and/or current diabetes medication. Study-specific HIV screening was conducted. The prevalence of diabetes was 9.2% (54/589, 95%CI: 7.0–11.8%) with 52% newly diagnosed. Moderate/severe undernutrition (body mass index (BMI) <17 kg/2) was 20.5% (130/634, 95%CI: 17.4–23.9%). Forty percent of participants had at least one co-morbidity (diabetes, moderate/severe undernutrition or moderate/severe anaemia (haemoglobin <11 g/dL)). HIV infection (24.4%, 74/303) was not associated with other co-morbidities (but high refusal in rural clinics). Central obesity assessed by waist-to-hip ratio was more strongly associated with diabetes (Adjusted Odds Ratio (AOR) = 6.16, 95%CI: 3.15–12.0) than BMI. Undernutrition was less common in men (AOR = 0.44, 95%CI: 0.28–0.70), and associated with previous history of TB (AOR = 1.97, 95%CI: 1.28–3.04) and recent reduced food intake. The prevalence of multimorbidity was high demonstrating a significant unmet need. HIV was not a risk factor for increased non-communicable multimorbidity.

357 Utilizing a Health Information Exchange to Improve Care Transitions After an Emergency Department Visit

Improving care transitions for ambulatory sensitive conditions such as diabetes between the ED and primary care is important to patient safety. Health information exchanges (HIEs) may be useful tools in this process, although data demonstrating this impact is lacking. The primary objective of this study was to assess the feasibility of implementing a tailored care plan in the emergency department Information Exchange (EDIE), a statewide emergency department HIE and care coordination platform endorsed by the American College of Emergency Physicians. We hypothesize that patients who receive this intervention will have decreased ED visits and increased contacts with primary care providers after an ED visit compared to patients who did not receive the intervention. We performed a randomized parallel experimental study with a pre-post design. A total of 260 patients who were attributed to one of four primary care clinics within the University of Washington system, had a diagnosis of diabetes and had at least one ED visit were randomly assigned to the CARE (Coordination and Referral from Emergency) intervention or a control arm. CARE included a tailored care plan in the EDIE which is a care coordination HIE platform that is used in all EDs in Washington and across 22 states. The care plan included primary care clinic information, current diabetes medications, and HgA1c values and was pushed to emergency providers at the time a patient checked in to any ED that utilizes EDIE. Care plans were updated weekly. Measured outcomes included statewide ED visits and primary care clinic contacts within 10-days of an ED visit. These outcomes were compared using “differences in differences” models 12 months pre- and post-intervention. Overall, the number of ED visits decreased significantly in the post-intervention period (mean ratio: 0.75, p=0.002). The decrease was statistically significant in the intervention group (0.66, p=0.003) while the decrease in the control group was non-significant (0.83, p=0.10) over the same period. Similarly, the rate of primary care provider contacts after an ED visit decreased significantly overall (odds ratio: 0.76, p=0.048). In this case the decrease was statistically significantly in the control group (0.68, p=0.018) but not in intervention group (0.86, p=0.45). However, the difference in differences was not significant for either ED visits (p=0.11) or clinic contacts (p=0.37). Results were similar when adjusting for site, sex, age, and English as primary spoken language. Overall implementation of tailored care plans within a HIE care coordination platform is feasible. Patients with diabetes and previous ED visits with a tailored care plan in a statewide care coordination HIE had fewer ED visits after implementation. However, differences in post-period ED visits and clinic contacts were not statistically significant between experimental and control groups.

Prevalence, awareness, and determinants of type 2 diabetes mellitus among commercial taxi drivers in buffalo city metropolitan municipality South Africa: A cross-sectional survey.

Undiagnosed type 2 diabetes mellitus constitutes a significant threat to the health of commercial taxi drivers, safety of the passengers and other road users. This study determines the prevalence of pre-diabetes and type 2 diabetes mellitus among commercial taxi drivers in Buffalo City Metropolitan Municipality (BCMM), Eastern Cape and examines the factors associated with type 2 diabetes mellitus.A cross-sectional survey of 403 commercial taxi drivers was undertaken using the World Health Organization (WHO) STEPwise approach. Anthropometric, blood pressure, and blood glucose measurements followed standard procedure. Diabetes status was determined using the fasting blood glucose (FBG) test. Diabetes was defined as a FBG ≥7.0mmol/L or self-reported history of diabetes or current diabetes medication use (treatment), while pre-diabetes was defined as a FBG of 5.6 to 6.9 mmol/L. Awareness of diabetes was defined as a self-reported history of diabetes.The mean age of the study participants was 43.3 ± 12.5years. Prevalence of pre-diabetes and diabetes were 17% (95% CI: 13.4–20.6) and 16% (95% CI: 12.4–19.6), respectively. Of those who had diabetes (n = 63), the majority were aware of their diabetes status (n = 43) and were on treatment (n = 30). In the unadjusted logistic regression, age, ever married, hypertension, obesity, and driving for more than 5 years were independently associated with diabetes. However, only age >35 (adjusted odds ratio [AOR]= 3.65, CI: 1.17–11.32), ever married (AOR= 3.26, CI: 1.52–6.99) and hypertension (AOR= 3.23, CI: 1.56–6.69) were associated with diabetes in the adjusted logistic regression model.The prevalence of diabetes among commercial taxi drivers in this study is high, almost twice the national prevalence of diabetes in South Africa. Periodic health screening among this sub-population group is important to bridge the gap of undiagnosed diabetes in South Africa.

The role of joint working between primary and secondary care in supporting people with type 1 diabetes

The role of joint working between primary and secondary care in supporting people with type 1 diabetes

Patients’ Future Expectations for Diabetes and Hypertension Treatments: “Through the Diet… I Think This is Going to Go Away.”

Diabetes and hypertension are chronic conditions for which over 90% of patients require medication regimens that must be intensified over time. However, delays in intensification are common, and may be partially due to unrealistic patient expectations. To explore whether patient expectations regarding their diabetes and hypertension are congruent with the natural history of these conditions. Qualitative analysis of semi-structured interviews. Sixty adults from an urban academic primary care clinic taking oral medications for both diabetes (duration <10years) and hypertension (any duration) MAIN MEASURES: (1) Expectations for their a) current diabetes and hypertension medications, b) need for additional medications, c) likelihood of cure (not requiring medications); (2) preferences for receiving information on expected duration of treatments KEY RESULTS: The average patient age was 60years, and 65% were women. Nearly half (48%) of participants expected to discontinue current diabetes medications in 6years or less, whereas only one-fifth (22%) expected to take medications for life. For blood pressure medications, one-third (37%) expected to stop medicines in 6years or less, and one-third expected to take medicines for life. The vast majority did not expect that they would need additional medications in the future (oral diabetes medications: 85%; insulin: 87%; hypertension medications: 93%). A majority expected that their diabetes (65%) and hypertension (58%) would be cured. Most participants believed that intensifying lifestyle changes would allow them to discontinue medications, avoid additional medications, or cure their diabetes and hypertension. Nearly all participants (97%) wanted to hear information on the expected duration of their diabetes and hypertension treatments from their healthcare provider. Providers should educate patients on the natural history of diabetes and hypertension in order to manage patient expectations for current and future medications. Future research should assess whether education can increase the adoption of and adherence to medications, without diminishing enthusiasm for lifestyle changes.

A Genome-Wide Association Study Uncovers a Genetic Locus Associated with Thoracic-to-Hip Ratio in Koreans.

The thoracic-to-hip circumference ratio (THR) is an anthropometric marker recently described as a predictor of type 2 diabetes. In this study, we performed a genome-wide association study (GWAS) followed by confirmatory analyses to identify genetic markers associated with THR. A total of 7,240 Korean subjects (4,988 for the discovery stage and 2,252 for the confirmatory analyses) were recruited for this study, and genome-wide single nucleotide polymorphism (SNP) genotyping of the initial 4,988 individuals was performed using Affymetrix Human SNP array 5.0. Linear regression analysis was then performed to adjust for the effects of age, sex, and current diabetes medication status on the THR of the study subjects. In the initial discovery stage, there was a statistically nominal association between minor alleles of SNP markers on chromosomes 4, 8, 10, and 12, and THR changes (p < 5.0 × 10−6). The subsequent confirmatory analyses of these markers, however, only detected a significant association between two SNPs in the HECTD4 gene and decreased THRs. Notably, this association was detected in male (rs11066280: p = 1.14 × 10−2; rs2074356: p = 1.10 × 10−2), but not in female subjects. Meanwhile, the combined results from the two analyses (initial and confirmatory) indicated that minor alleles of these two intronic variants exhibited a significant genome-wide association with decreased THR in the male subjects (n = 3,155; rs11066280: effect size = −0.008624, p = 6.19 × 10−9; rs2074356: effect size = −0.008762, p = 1.89 × 10−8). Furthermore, minor alleles of these two SNPs exhibited protective effects on patients’ risks for developing type 2 diabetes. In conclusion, we have identified two genetic variations in HECTD4 that are associated with THR, particularly in men.

Explaining psychological insulin resistance in adults with non-insulin-treated type 2 diabetes: The roles of diabetes distress and current medication concerns. Results from Diabetes MILES—Australia

AimsTo investigate the contribution of general and diabetes-specific emotional wellbeing and beliefs about medicines in the prediction of insulin therapy appraisals in adults with non-insulin-treated type 2 diabetes. MethodsThe sample included Diabetes MILES–Australia cross-sectional survey participants whose primary diabetes treatment was oral hypoglycaemic agents (N=313; 49% women; mean±SD age: 57±9 years; diabetes duration: 7±6 years). They completed validated measures of beliefs about the ‘harm’ and ‘overuse’ of medications in general (BMQ General); ‘concerns’ about and ‘necessity’ of current diabetes medications (BMQ Specific); negative insulin therapy appraisals (ITAS); depression (PHQ-9); anxiety (GAD-7), and diabetes distress (DDS-17). Factors associated with ITAS Negative scores were examined using hierarchical multiple regressions. ResultsTwenty-two percent of the variance in ITAS Negative scores (52±10), was explained by: number of complications (β=−.15, p=.005), DDS-17 subscale ‘emotional burden’ (β=.23, p<.001), and ‘concerns’ about current diabetes treatment (β=.29, p<.001). General beliefs about medications and general emotional wellbeing did not contribute significantly to the model. ConclusionsPsychological insulin resistance may reflect broader distress about diabetes and concerns about its treatment but not general beliefs about medicines, depression or anxiety. Reducing diabetes distress and current treatment concerns may improve attitudes towards insulin as a potential therapeutic option.

Recent and Emerging Therapeutic Medications in Type 2 Diabetes Mellitus

Nearly 285 million people worldwide, with 10% being Americans, suffer from diabetes mellitus and its associated comorbidities. This is projected to increase by 6.5% per year, with 439 million inflicted by year 2030. Both morbidity and mortality from diabetes stem from the consequences of microvascular and macrovascular complications. Of the 285 million with diabetes, over a quarter of a million die per year from related complications, making diabetes the fifth leading cause of death in high-income countries. These startling statistics illustrate the therapeutic failure of current diabetes drugs to retard the progression of diabetes. These statistics further illustrate the continual need for further research and development of alternative drugs with novel mechanisms to slow disease progression and disease complications. The treatment algorithm updated in 2008 by American Diabetes Association and the European Association for the Study of Diabetes currently recommends the traditional medications of metformin, either as monotherapy or in combination with sulfonylurea or insulin, as the preferred choice in the tier 1 option. The algorithm only suggests addition of alternative medications such as pioglitazone and incretin-based drugs as second-line agents in the tier 2 "less well-validated" option. However, these traditional medications have not proven to delay the progressive course of diabetes as evidence of increasing need over time for multiple drug therapy to maintain sufficient glycemic control. Because current diabetes medications have limited efficacy and untoward side effects, the development of diabetes mellitus drugs with newer mechanisms of action continues. This article will review the clinical data on the newly available incretin-based drugs on the market, including glucagon-like peptide agonists and of dipeptidyl peptidase type-4 inhibitors. It will also discuss 2 unique medications: pramlintide, which is indicated for both type and type-2 diabetes, and colesevelam, which is approved by the United States Food and Drug Administration for both type-2 diabetes and hyperlipidemia. It will further review the clinical data on the novel emerging agents of sodium-glucose cotransporter-2 inhibitors, tagatose, and succinobucol, all currently in phase III clinical trials. This review article can serve as an aid for clinicians to identify clinical indications in which these new agents can be applied in the treatment algorithm.

Vascular Protective Effects of Diabetes Medications that Mimic or Increase Glucagon-Like Peptide-1 Activity

The incidence of type 2 diabetes (T2DM) is increasing rapidly worldwide and is a strong risk factor for cardiovascular disease (CVD) events. Although hyperglycemia is associated with increased CVD, intensive glycemic control with current diabetes medications has failed in recent large clinical trials to reduce macrovascular disease, demonstrating that intensive glucose control alone is insufficient to reduce major CVD events. A new approach to lowering glucose takes advantage of the incretin system and medications that raise or mimic glucagon-like peptide-1 (GLP-1). These agents not only improve glycemic control by mechanisms that minimize hypoglycemia, but also improve lipoprotein profiles, blood pressure control and weight loss. There is also increasing evidence that at least pharmacologic concentrations of GLP-1 or GLP-1 mimetics may improve endothelial function and have direct vascular-protective effects. Importantly, these benefits transpired even before the improvements in weight and overall glucose control occurred. It remains to be seen whether the chronic effects of GLP-1 activity on glucose, CVD risk factors and vascular function will lead to lasting beneficial effects on CVD risk. If preliminary findings on the vasculoprotective effects of GLP-1 agents are validated and confirmed in longitudinal clinical trials, this class of drugs may represent a paradigm shift in the treatment of vascular disease in both patients with diabetes and in non-diabetic individuals at high risk for CVD. Recent patents regarding GLP-1 agents are discussed in this review article.

Hypoglycemia in Type 2 Diabetes—Consequences and Risk Assessment

Although hypoglycemia has traditionally been considered a significant complication of the treatment of type 1 diabetes, the greater incidence of type 2 diabetes compared with type 1, the intensive treatment strategies currently employed, and the longer life expectancy of patients with diabetes, give rise to a large number of type 2 patients at risk for hypoglycemia. This number is likely to rise in an aging population with the increasing use of insulin to treat diabetes. The highest incidence of hypoglycemia is seen in older patients with poor glycemic control and is associated with the use of antidiabetic agents that increase blood insulin concentrations independently of blood glucose concentration (oral antidiabetic drugs or exogenous insulin). Hypoglycemia has a substantial clinical impact in terms of mortality, morbidity, and quality of life. The economic impact of severe hypoglycemic events owing to direct hospital costs and the indirect costs of the inability to work are considerable. Furthermore, both patients’ and physicians’ fear of hypoglycemia reduces adherence to therapeutic regimens and limits the ability of current diabetes medications to achieve the level of glycemic control required to prevent disease progression. Newer therapies and improvements in patient education may help patients achieve improved glucose control by safely reducing glycosylated hemoglobin (HbA1c) with a lower risk of hypoglycemia.

SGLT2 inhibition — a novel strategy for diabetes treatment

Inhibiting sodium-glucose co-transporters (SGLTs), which have a key role in the reabsorption of glucose in the kidney, has been proposed as a novel therapeutic strategy for diabetes. Genetic mutations in the kidney-specific SGLT2 isoform that result in benign renal glycosuria, as well as preclinical and clinical studies with SGLT2 inhibitors in type 2 diabetes, support the potential of this approach. These investigations indicate that elevating renal glucose excretion by suppressing SGLT2 can reduce plasma glucose levels, as well as decrease weight. Although data from ongoing Phase III trials of these agents are needed to more fully assess safety, results suggest that the beneficial effects of SGLT2 inhibition might be achieved without exerting significant side effects--an advantage over many current diabetes medications. This article discusses the role of SGLT2 in glucose homeostasis and the evidence available so far on the therapeutic potential of blocking these transporters in the treatment of diabetes.

Hypoglycaemia in Type 2 diabetes

The primary cause of hypoglycaemia in Type 2 diabetes is diabetes medication—in particular, those which raise insulin levels independently of blood glucose, such as sulphonylureas (SUs) and exogenous insulin. The risk of hypoglycaemia is increased in older patients, those with longer diabetes duration, lesser insulin reserve and perhaps in the drive for strict glycaemic control. Differing definitions, data collection methods, drug type/regimen and patient populations make comparing rates of hypoglycaemia difficult. It is clear that patients taking insulin have the highest rates of self-reported severe hypoglycaemia (25% in patients who have been taking insulin for > 5 years). SUs are associated with significantly lower rates of severe hypoglycaemia. However, large numbers of patients take SUs in the UK, and it is estimated that each year > 5000 patients will experience a severe event caused by their SU therapy which will require emergency intervention. Hypoglycaemia has substantial clinical impact, in terms of mortality, morbidity and quality of life. The cost implications of severe episodes—both direct hospital costs and indirect costs—are considerable: it is estimated that each hospital admission for severe hypoglycaemia costs around £1000. Hypoglycaemia and fear of hypoglycaemia limit the ability of current diabetes medications to achieve and maintain optimal levels of glycaemic control. Newer therapies, which focus on the incretin axis, may carry a lower risk of hypoglycaemia. Their use, and more prudent use of older therapies with low risk of hypoglycaemia, may help patients achieve improved glucose control for longer, and reduce the risk of diabetic complications.Diabet. Med. 25, 245–254 (2008)

Case Study: Symptoms in a Diabetes Client: Type 1, Type 2, or Type 1.5?

W.G. is a 41-year-old white man who was diagnosed with diabetes 15 months ago. He is now beginning diabetes education and medical nutrition therapy (MNT) to gain weight upon referral from his primary care physician. His most recent hemoglobin A1c (A1C) was 5.0%. His current diabetes medication is metformin (Glucophage), 500 mg with breakfast, and he was started on pioglitazone (Actos) 2 weeks ago. He takes no other medications; denies smoking, alcohol, and drug use; and knows of no health problems other than diabetes. His history revealed a blood glucose level >500 mg/dl at the time of diagnosis, with negative ketones. He checked ketones occasionally in the first year of diabetes, and all tests were negative. His mother had diabetes and was on insulin. He reports that he was on glimepiride (Amaryl) during the first year of diabetes, but that it was discontinued when he was started on metformin. He complains of frequent urination, hunger, and thirst, which leads to drinking more than 1 gallon of water daily. He is very concerned because he is often agitated, anxious, and impatient to the point that it is affecting his family and work life. He was employed as a technician but is on leave until he feels better. His physician prescribed alprazolam (Xanax) for anxiety, but he did not fill the prescription. Physical assessment reveals a height of 74 inches, …