SP - Diabetes

Introduction: The representation of frailty in type 2 diabetes trials is unclear. This study used individual patient data (IPD) from trials of newer glucose-lowering therapies to quantify frailty and assess the association between frailty and treatment efficacy and adverse events. 

Methods: We analysed IPD from 34 trials of sodium glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor analogues and dipeptidyl peptidase-4 inhibitors. Frailty was quantified using a cumulative deficit frailty index (FI). For each trial we assessed the distribution of the FI; interactions between frailty and treatment efficacy (HbA1c and major adverse cardiovascular events [MACE]); and associations between FI and non-completion, adverse events, and hypoglycaemic episodes before pooling results using random-effects network meta-analysis. 

Findings: Trial participants numbered 25,208. Mean age 53.8-74.2 years. Median frailty prevalence (FI>0.24) was 1.9% (IQR 0.8% to 6.1%). There was no heterogeneity in treatment efficacy by FI for MACE or HbA1c in the primary analysis (high uncertainty for MACE). A 0.1-point increase in the FI was associated with adverse events (incidence rate ratio, IRR 1.43, 95% confidence interval 1.34-1.53), treatment-related adverse events (1.35, 1.22-1.50), serious adverse events (2.04, 1.80-2.30), hypoglycaemia (1.18, 1.04-1.34), MACE (hazard ratio 3.02, 2.49-3.68) and early withdrawal (odds ratio 1.45, 1.30-1.62). 

Conclusions: Frailty is associated with similar efficacy of treatment but with greater incidence of both adverse events and MACE. Frailty was rare in most trials. While these findings support calls to relax HbA1c-based targets in people living with frailty, they also highlight the need for inclusion of people living with frailty in trials.
 

Background: Newer glucose-lowering agents for type 2 diabetes (sodium glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor analogues (GLP1ra) and dipeptidyl peptidase-4 inhibitors (DPP4i)) improve hyperglycaemia and SGLT2i and GLP1ra reduce the risk of major adverse cardiovascular events (MACE). It is not clear whether the efficacy of these agents varies by age.

Methods: We searched Medline and Embase, plus clinical trial registries, for randomised controlled trials of SGLT2i, GLP1ra and DPP4i, versus placebo or active comparator, in adults with type 2 diabetes.

Outcomes: HbA1c and MACE. Where IPD were available, we modelled age-treatment interactions for each trial. Otherwise, we assessed age distributions along with results from aggregate trial data. IPD and aggregate findings were combined in a Bayesian network meta-analysis to assess whether the efficacy differed by age.

Results: We identified 616 eligible trials (604 reporting HbA1c, 23 reporting MACE) and obtained IPD for 75 trials (6 reporting MACE). Mean age was 59.0 (10.7) years and 64.0 (8.6) in HbA1c and MACE trials, respectively. SGLT2i reduced HbA1c by 0.5-1.0% overall compared to placebo. This reduction versus placebo was attenuated in older participants (change in HbA1c 0.25 percentage-points less for 75-year-olds compared to 45-year-olds). SGLT2i showed greater relative efficacy in MACE risk reduction among older than younger people. This finding was sensitive to the exclusion of one of the IPD MACE trials, however, in all sensitivity analyses, SGLT2i were either as efficacious or more efficacious in older participants. There was no consistent difference in efficacy by age for GLP1ra or DPP4i for HbA1c or MACE.

Conclusion: Newer glucose-lowering drugs are efficacious across age and sex groups. SGLT2i are more cardioprotective in older than younger people despite smaller HbA1c reductions. Age alone should not be a barrier to treatments with proven cardiovascular benefit providing they are well tolerated align with patient priorities.

Background:

Type 2 Diabetes mellitus (T2DM) is the most common long-term metabolic condition in older people. In the UK, half of all diabetic patients are over 65 and prevalence reaches 10% in over 75s. Lifestyle interventions reduce diabetic complications and can achieve remission, however, there are concerns over the generalisability of these findings to the diabetic population, particularly elderly, complex patients, and those from ethnic minorities. This systematic review quantifies the disparity between diabetes clinical trial cohorts and the UK diabetic population.

Method:

This is a systematic review of UK-based randomised control trials (RCTs) of non-pharmaceutical interventions in adults with T2DM. Data was collected on characteristics of participants included in these studies, including age, sex, ethnicity, socioeconomic status and education of participants.

Results:

Our search strategy identified 5437 results, of which 161 met the criteria for full-text screening. After full-text screening and de-duplication, 80 RCTs were included in our analysis. Of 80 studies, 60% (48/80) reported a mean participant age under 60. Only 40 (50%) reported participant age range; of these the maximum participant age was under 65 in 20% and under 75 in 60%. Where the mean age of participants was over 60, 56% (18/32) restricted participation by comorbidities. Almost all of these precluded anyone with pre-existing CVD (17/18), one third precluded any comorbidities, and 5/18 precluded hypertensive patients. Only 26% of studies reported the ethnicity of participants. These cohorts were not representative of the UK diabetic population, with underrepresentation of Asian ethnic groups in 90% of trials.

Conclusions:

Representation of elderly patients with comorbidities and those belonging to ethnic minority groups is severely limited in UK based T2DM RCTs of lifestyle interventions. Failure to include a representative population in clinical trial cohorts risks guidance that is not generalisable to the UK diabetic population, potentially exacerbating existing health inequities.

Older people with diabetes are often admitted with falls, dizziness or confusion that may stem from undiagnosed episodes of hypoglycaemia. We examined the use of a 10-day period of round the clock glucose monitoring (CGM), to detect hypoglycaemia in older people with diabetes with symptoms potentially related to hypoglycaemia. 

Methods 

Population: Age 75 years and older, on sulfonylureas and/or insulin, presenting to hospital with a fall and/or symptoms suggestive of unrecognised hypoglycaemia. 

Design: Single-centre, observational study (no change to standard diabetes care). Intervention: 10 days of CGM with Dexcom G6 sensor and Android app on smartphone to continuously transmit data. 

Primary outcomes: Proportion of participants with captured hypoglycaemia; within that group, time spent in the hypoglycaemic range (Battelino T, Danne T, Biester T, et al. Diabetes Care. 2019;42(8):1593-603.). 

Secondary outcomes: Overall time in range; emergency department re-attendances and/or hospital re-admissions for falls, fractures, heart attacks, ischaemic strokes and death within 30 days. REC IRAS project ID: 301286. 

Results 

26 eligible participants of which 13 consented to participate. At the time of writing, nine participants (mean age 81 years) completed the study.

There were no reports of pain or skin reactions from the participants.

Hypoglycaemic events were captured in 3 of 9 participants, with two participants suffering >1 hour below 3.9mmol/L. Only 3 participants achieved >50% time in range target (3.9-10.0mmol/L). 

Discussion 

We have detected significant hypoglycaemic episodes in our participants. CGM should be used more widely in older patients with diabetes who present with falls, dizziness or confusion. 

Limitations include issues around data capture due to participants struggling to navigate the mobile phone app. Despite this, all participants felt that CGM was better than finger-prick glucose testing. Future work is needed to explore how CGM can be deployed after acute admissions in this patient group.

INTRODUCTION

Type 2 diabetes mellitus (T2DM) is associated with poor health outcomes (1) and few people aged >70 years likely benefit from HbA1c <53mmol/mol(2) with ≤64mmol/mol generally accepted in people with moderate-severe frailty. We analysed fallers with T2DM to evaluate their outcomes and frailty status.

METHODS

Older Persons Assessment Service (OPAS) is an Emergency Department service which accepts patients on frailty criteria (aged >70 years, falls, confusion, care dependence, polypharmacy and poor mobility). OPAS databank was retrospectively analysed for people with T2DM admitted with a fall June 2020 to April 2022. Interactions between clinical outcomes with therapeutic agents used, age, Charlson Co-morbidity index (CCMI) and Clinical Frailty Score (CFS) were evaluated.

RESULTS

Six-hundred and seventy-nine patients were assessed; 191 (28.1%) had diabetes with a mean HbA1c 56.7 (IQR: 43.0 – 61.5) mmol/mol, 245 (36.1%) were male. Patients with diabetes had a similar mean CFS (5.3 vs 5.3, p=0.52) and age (83.8 vs 83.2 years, p=0.28) as those without diabetes, but had a higher mean CCMI (5.0 vs 7.0, p<0.001). People with diabetes were more likely to die within 12 months (31.4% vs 25%, p<0.05), and there was a trend to greater mortality in patients with diabetes who used insulin and/or gliclazide compared to those who used other agents (49.6% vs 30.9%, p=0.12).

CONCLUSIONS

Falls are a significant burden, and hypoglycaemic agents may contribute to the greater mortality observed in people with diabetes. Clinician awareness of the poorer prognosis associated with diabetes to support de-prescribing diabetes therapies (2) for patients with significant frailty and HbA1c <64mmol/mol. A frailty assessment should be part of any interaction(3) in the older T2DM patient. We are currently writing a local guideline on Diabetes management in Older Adults in Swansea Bay UHB.