Endocrinology and Diabetes

Microvascular Outcomes of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists in Type 2 Diabetes: A Systematic Review of Retinopathy and Nephropathy Evidence (2025)

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Type of publication:

Systematic Review

Author(s):

Arif, Atia; Lama, Sanu; Singla, Bhavna; Singla, Shivam; Kumawat, Sunita; Tharwani, Anusha; Usman, Muhammad; Khalid, Hamna; Kanukollu, Venkata Madusudana Rao; *Ekomwereren, Osatohanmwen; Khan, Shabir.

Citation:

Cureus. 17(9):e92976, 2025 Sep.

Abstract:

This systematic review evaluated randomized controlled trials examining the effects of glucagon-like peptide-1 (GLP-1) receptor agonists on microvascular outcomes in type 2 diabetes, focusing on diabetic retinopathy and nephropathy. Four eligible RCTs, enrolling over 27,000 patients with follow-up periods ranging from 32 weeks to 5.4 years, were included. GLP-1 receptor agonists consistently demonstrated renal protective effects, primarily driven by reductions in new or worsening nephropathy and acroalbuminuria, with more modest and inconsistent effects on estimated glomerular filtration rate (eGFR) decline. In contrast, their impact on retinopathy remained inconclusive. A transient signal of worsening retinopathy has been reported in the context of rapid glycemic improvement; however, across large outcome trials, effects on retinopathy have been inconsistent and remain inconclusive. Overall, the evidence for retinopathy risk is limited by small event numbers, heterogeneity in assessments, and exploratory analyses. The certainty of renal benefit was strengthened by rigorous trial designs and low risk of bias, whereas retinopathy outcomes were generally secondary and less robust. These findings suggest that GLP-1 receptor agonists can be prioritized for patients at high renal risk, but careful monitoring of individuals with pre-existing retinopathy remains warranted

DOI: 10.7759/cureus.92976

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Streamlining Patient Care in Endocrinology: A Consolidated Handover Tool (2025)

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Type of publication:

Service improvement case study

Author(s):

*Dr Krishna Iyer; *Dr Lauren Morris

Citation:

SaTH Improvement Hub, April 2025

SMART Aim:

To improve communication of patient details and reduce hospital stays by April 2025, as evidenced by doctor satisfaction with handovers and shorter discharge times.

Link to PDF poster

Real-World Outcomes of Transition From CGM-Augmented Non-Closed Loop (NCL) Omnipod Dash To Omnipod 5 Hybrid Closed Loop (HCL) Continuous Subcutaneous Insulin Infusion (CSII) in Adult Type 1 Diabetes(T1D) (2025)

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Type of publication:

Conference abstract

Author(s):

*Basavaraju N.; *Cane C.; *Cooksey M.; *Wilkes V.; *Brown H.; *Jones A.; *Moulik P.;

Citation:

Diabetes Technology and Therapeutics. Conference: 18th International Conference on Advanced Technologies and Treatments for Diabetes, ATTD 2025. Amsterdam Netherlands. 27(Supplement 2) (pp e179), 2025. Date of Publication: 01 Feb 2025.

Abstract:

Background and Aims: HCL CSII has recently been commissioned nationally by NHS England for type1 diabetes (T1D). We looked into the impact of transitioning from CGMaugmented non-closed loop (NCL) CSII to HCL CSII with the same insulin delivery system. Method(s): We analysed a database of T1D on CSII managed in a single district general hospital under one Consultant Diabetologist team. Patients were on Omnipod DASH with Freestyle Libre2/DexcomG6 CGM and transitioned to Omnipod 5 with Dexcom G6 with built in SmartAdjustTM technology. Data was analysed with paired sample T-test (SPSS) at baseline and 6months. Result(s): 53 patients were included, with 31females (59%) and 22males (41%). Baseline mean age was 47years (20-80), diabetes duration 24years (5-62), BMI 27.6kg/m2 (20-41), HbA1c 55-mmol/mol (30-80). At 6 months, mean weight increased by 1.2-kg (p=0.04), BMI increased by 0.2kg/m2 (p=0.617), HbA1c reduced by 3.4mmol/mol (p=0.002), Time in range: TIR (glucose 3.9-10mmol/L) improved from 63% to 71% (p <0.005). GOLD score remained unchanged at 2.0. Serum creatinine increased from 77 to 80umol/L (p=0.007), eGFR reduced from 92 to 80ml/ min (p<0.001), mean urine microalbumin, total cholesterol, grading of retinal screening remained unchanged. Diabetes Treatment Satisfaction Questionnaire, hypoglycaemia fear survey scores were unchanged and mean INSPIRE (Insulin delivery Systems: Perceptions, Ideas, Reflections and Expectations) score was 77 (40-100). Conclusion(s): This analysis demonstrates statistically significant improvement in glycaemic parameters (HbA1c and TIR) at 6 months with minimal but statistically significant weight loss. There were no significant changes in retinal screening but surprisingly some reduction in renal function was observed. Quality of life questionnaires remained unchanged but INSPIRE questionnaire for automated insulin delivery (AID) showed promising results.

DOI: 10.1089/dia.2024.78502.abstracts

Ambulatory Glucose Profile (AGP) Improvements Occur Early During Transition From Sensor Augmented Omnipod Dash to Hybrid Closed Loop Omnipod 5 in Adults With Type 1 Diabetes(T1D) (2025)

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Type of publication:

Conference abstract

Author(s):

*Basavaraju N.; *Cane C.; *Cooksey M.; *Brown H.; *Wilkes V.; *Jones A.; *Moulik P.;

Citation:

Diabetes Technology and Therapeutics. Conference: 18th International Conference on Advanced Technologies and Treatments for Diabetes, ATTD 2025. Amsterdam Netherlands. 27(Supplement 2) (pp e174-e175), 2025. Date of Publication: 01 Feb 2025.

Abstract:

Background and Aims: Significant glycaemic benefits with hybrid closed loop(HCL) continuous subcutaneous insulin infusion (CSII) over sensor augmented non-closed loop CSII must be balanced against the risks of worsening retinopathy and treatment induced neuropathy in diabetes (TIND). Method(s): We analysed a database of T1D on CSII managed in a single district general hospital. Patients on Omnipod DASH with Freestyle Libre2/DexcomG6 CGM transitioned to Omnipod 5(OP5) with Dexcom G6 with built in SmartAdjustTM technology. All patients had a target glucose of 6.1mmol/L on OP5. AGP data were analysed with paired sample T-test (SPSS) at baseline, 3months and 6months. Result(s): 53 patients (31females and 22males) with mean age 47years (20-80), diabetes duration 24years (5-62), BMI 27.6kg/m2 (20-41), HbA1c 55mmol/mol(30-80) were included. Conclusion(s): There was statistically significant and rapid improvement in GMI, level 1 & level 2 TAR, TIR and level 1 TBR between 0 and 3 months, sustained at 6 months but no significant change between 3 and 6 months. The early and rapid improvement in glycaemic control post HCL highlights the need for close monitoring of worsening retinopathy in the first year.

DOI: 10.1089/dia.2024.78502.abstracts

Treatment-Induced Neuropathy in Diabetes Post Use of Hybrid Closed Loop Continuous Subcutaneous Insulin Infusion in Type 1 Diabetes (2025)

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Type of publication:

Conference abstract

Author(s):

*Basavaraju N.; *Beard N.; *Jones A.; *Moulik P.;

Citation:

Diabetes Technology and Therapeutics. Conference: 18th International Conference on Advanced Technologies and Treatments for Diabetes, ATTD 2025. Amsterdam Netherlands. 27(Supplement 2) (pp e264-e265), 2025. Date of Publication: 01 Feb 2025.

Abstract:

Background and Aims: Treatment-induced neuropathy in diabetes(TIND) is a transient, painful peripheral neuropathy occasionally with autonomic component, occurring with rapid glycaemic improvement. Hybrid closed loop(HCL) continuous subcutaneous insulin infusion(CSII) in type 1 diabetes(T1D) can improve glucose levels rapidly. Method(s): Retrospective review of two cases. Case 1: 27- year-old male, T1D for 16years, disengagement, maculopathy switched from basal-bolus insulin to HCL-CSII(Omnipod5- DexcomG6). Case 2: 44-year-old female, T1D for 42years, disengagement laser treated retinopathy, neuropathy, toe amputation switched from basal-bolus insulin to HCL-CSII(Omnipod5- DexcomG6). Result(s): Case 1: Pre-HCL HbA1c107mmol/mol. 3months post HCL HbA1c 69mmol/mol. He reported neuropathic pain in lower limbs, commenced amitriptyline for 3months with resolution. He also developed proliferative retinopathy. Case 2: Pre- HCL HbA1c96mmol/mol improved to 54mmol/mol in 6months. She developed severe neuralgic pain in both feet, improved with Pregabalin for 3months. There was no deterioration in retinopathy. Conclusion(s): TIND is more common in T1D, pathophysiology may be endoneurial ischaemia and microvascular changes due to relative hypoglycaemic state. Diagnostic criteria include (i)decrease in HbA1c by 2%(22mmol/mol) over 3months (ii)neuropathic pain and/or autonomic symptoms within 8weeks after decrease in HbA1c (iii)acute onset of neuropathic pain and/ or autonomic dysfunction for more than 2weeks requiring medical attention. It is self-limiting, lasting from weeks to months. Symptomatic treatment include antiepileptics(pregabalin) and tricyclic antidepressants are effective. There are no reported cases of TIND with HCL-CSII in literature. Our two cases highlight TIND, like worsening retinopathy, is a potential complication of rapid improvement in glycaemic control with HCL-CSII in patients with pre-existing hyperglycaemia and patients' needs counselling about the potential short-term risks.

DOI: 10.1089/dia.2024.78502.abstracts

Is There a Correlation Between Hybrid Closed Loop(HCL) Continuous Subcutaneous Insulin Infusion(CSII) Glycaemic Improvement in Type 1 Diabetes(T1D) and Worsening Sensorineural Hearing Loss? - A Case Report (2025)

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Type of publication:

Conference abstract

Author(s):

*Basavaraju N.; *Jones A.; *Wilkes V.; *Moulik P.

Citation:

Diabetes Technology and Therapeutics. Conference: 18th International Conference on Advanced Technologies and Treatments for Diabetes, ATTD 2025. Amsterdam Netherlands. 27(Supplement 2) (pp e265), 2025. Date of Publication: 01 Feb 2025.

Abstract:

Background and Aims: T1D is associated with various comorbidities including sensorineural hearing loss (SNHL). HCL CSII treatment in T1D improves glucose levels rapidly. This may cause short-term worsening of retinopathy and neuropathy (treatment-induced neuropathy in diabetes). We present a case of T1D on HCL CSII with worsening hearing loss. Method(s): A 46-year-old gentleman with T1D for 30 years with pre- proliferative retinopathy had mild right sided tinnitus and sensorineural hearing loss (on pure tone audiometry) diagnosed 8 years ago. MRI internal auditory meatus was normal. He was commenced on HCL CSII (Omnipod 5 with Dexcom G6). Result(s): Pre-HCL HbA1c was 75mmol/mol. Glucose management indicator (GMI) after 4weeks rapidly dropped to 53mmol/mol which further reduced to 48mmol/mol in 6months. He reported worsening of right sided tinnitus and hearing loss with development of new left sided tinnitus. He also developed maculopathy. Conclusion(s): Approximately 9.2/1000 people with T1D develop debilitating SNHL every year. In people aged 40-60- years with T1D, hearing threshold in high frequencies(4,000- 8,000Hz) was significantly higher (25-30dB) when compared to age-matched controls (5-10dB). The mechanisms are damage to outer and inner hair cells, loss of spiral ganglion neurons through apoptosis, thickening of basement membrane, and pathologies involving stria vascularis and spiral ligament of the cochlear lateral wall. Whilst causality cannot be inferred from this case, the temporal sequence of rapidly improved glycaemic control with worsening tinnitus and hearing loss raises a possibility of its association. This requires further study preferably with pure tone audiometry, in a randomised clinical trial setting.

DOI: 10.1089/dia.2024.78502.abstracts

A systematic review and network meta-analysis of interventions to preserve insulin-secreting beta cell function in people newly diagnosed with type 1 diabetes: results from randomised controlled trials of immunomodulatory therapies (2025)

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Type of publication:

Systematic Review

Author(s):

Beese, Sophie E; Price, Malcolm J; Tomlinson, Claire; Sharma, Pawana; Harris, Isobel M; Adriano, Ada; Quinn, Lauren M; Gada, Ritu; *Horgan, Thomas J; Maggs, Fiona; Burrows, Martin; Nirantharakumar, Krishnarajah; Thomas, G Neil; Andrews, Robert C; Moore, David J; Narendran, Parth.

Citation:

BMC Medicine. 23(1):351, 2025 Jul 01.

Abstract:

BACKGROUND: Type 1 diabetes is characterised by the immune-mediated destruction of pancreatic beta cells. We aimed to determine the effectiveness of immunotherapies for preserving residual beta cell function in newly diagnosed (stage 3) type 1 diabetes.

METHODS: Searches were carried out in MEDLINE, Embase, Cochrane CENTRAL and trial registries until 31st Jul 2024. RCTs of immunotherapies to preserve beta cells in newly diagnosed type 1 diabetes were included. Data were extracted using a bespoke, piloted extraction sheet. Risk of bias was assessed using Cochrane Risk of Bias Tool 1. A random effects network meta-analysis was undertaken in R. The primary outcome was C-peptide. Interventions were analysed by class.

RESULTS: Sixty trials were included (4597 patients, 32 intervention classes). Forty-one trials of 42 interventions were eligible for network meta-analysis. Eleven interventions demonstrated statistically significantly higher levels of C-peptide than placebo at 12 months, mesenchymal stem cells (autologous and Wharton's jelly-derived cells), azathioprine, interferon-alpha (5000 IU), autologous dendritic cells, anti-TNF golimumab, low-dose ATG, 3 mg 1-course anti-CD3 teplizumab, baricitinib, cyclosporin and 9/11 mg 2-course anti-CD3 teplizumab but with substantial heterogeneity present (I2 = 66%). Azathioprine ranked highest (median ranking 3rd); however, rankings demonstrated relatively wide confidence intervals and thus uncertainty in exact rank order of near adjacent therapies. Risk of bias assessment identified poor reporting, particularly in older trials, but few studies demonstrated high risk overall.

CONCLUSIONS: Eleven of 42 interventions demonstrated statistically significantly higher C-peptide levels than placebo at 12 months in the network meta-analysis. These results have identified the 11 most promising therapies trialled and help to direct future head-to-head clinical trials to support approvals for interventions to treat those newly diagnosed with type 1 diabetes. However, data for some interventions originated from small studies (mesenchymal stem cell therapies, azathioprine, autologous dendritic cells) and findings should be considered as hypothesis generating and interpreted with caution due to evidence heterogeneity.

SYSTEMATIC REVIEW REGISTRATION: The protocol for the systematic review was registered on PROSPERO, the international database of prospectively registered systematic reviews (registration: CRD42018107904).

DOI: 10.1186/s12916-025-04201-z

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Is this Acute Manifestation of Adrenal Crisis? (2025)

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Type of publication:

Journal article

Author(s):

*Nwaneri C.

Citation:

Acta Medica International. 12(1) (pp 66-71), 2025. Date of Publication: 01 Jan 2025.

Abstract:

Adrenal crisis is a life threatening complication of both primary and secondary adrenocortical insufficiency. The diagnosis of adrenal crisis requires a high index of suspicion, such as circulatory collapse, refractory hypotension, and metabolic acidosis. The clinical features are because of both mineralocorticoid and glucocorticoid deficiencies. The primary and initial treatment is intravenous cortisol therapy, and saline (sometimes glucose). Case presentation was used in this 43 year old woman who presented with dizziness, anorexia, vomiting, generalized weakness, and lethargy. She had a history of recent tuberculosis infection and was commenced on antituberculosis therapy, rifampicin. Her biochemical profile was suggestive of impending adrenal crisis. Her chest X ray and computed tomography were grossly normal. The patient recovered completely and was discharged home with the resolution of her deranged metabolic and electrolyte derangements. Appropriate specialist care is vital in patients with adrenal crisis, coupled with initial aggressive fluid resuscitation and acid base balance and good intensive care.

DOI: 10.4103/amit.amit_89_24

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Is Hybrid Closed Loop Continuous Subcutaneous Insulin Infusion Beneficial in Adults with Type 1 Diabetes(T1D) on Continuous Glucose Monitoring: A Reallife District General Hospital Perspective (2024)

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Type of publication:

Conference abstract

Author(s):

*Jones A.; *Basavaraju N.; *Cane C.; *Moulik P.

Citation:

Diabetes Technology and Therapeutics. Conference: Advanced Techologies and Treatments for Diabetes Conference, ATTD 2024. Virtual. 26(Supplement 2) (pp A275-A276), 2024. Date of Publication: 01 Feb 2024.

Abstract:

Background and Aims: Hybrid closed loop(HCL) continuous subcutaneous insulin infusion(CSII) and continuous glucose monitoring(CGM) have made significant improvements in management of T1D.We studied benefits of Hybrid closed loop(HCL) over non-closed loop(NCL) CSII in a cohort of adults with T1D. Method(s): We analysed a live database of patients managed in a single District General Hospital (DGH) service on CSII from 2011 onwards. %Time in range (TIR), %hypoglycaemia (%hypo) and HbA1c were analysed with independent samples T-Test (SPSS software). Result(s): 302 patients were included: mean age was 44 years (range 19-81), female:male 57:43, diabetes duration 25years (range 2-61), and mean pre-CSII HbA1c 63mmol/mol. 218 were on HCL, 21 partial closed loop(PCL) and 63 were NCL. All patients were either on real-time(rt)CGM or intermittently scanned( is)CGM. HCL users were on Medtronic 780G with Guardian G4 sensor or Tandem T-Slim with Dexcom G6 sensor and NCL patients mostly on Omnipod DASH with rtCGM or isCGM. For HCL vs NCL systems, mean HbA1c (52 vs 57mmol/mol, p < 0.005), TIR (71% vs 62%, p < 0.005) were significantly improved on HCL. There was a trend to reduced %hypo (1.64% vs 2.64%,p = 0.08) but not statistically significant. Conclusion(s): This analysis demonstrates significantly better glycaemic control, in both HbA1c and TIR parameters, in HCL CSII users compared to NCL CSII in T1D. Hypoglycaemia was reduced but did not achieve statistical significance, possibly due to overall low rate of hypoglycaemia in the entire cohort. We speculate patients would have been responding to CGM alarm warnings to abort actual hypoglycaemic events.

Is Continuous Glucose Monitoring (CGM) the Critical Technological Intervention in Adults with Type 1 Diabetes(T1D) on Continuous Subcutaneous Insulin Infusion (CSII) Therapy? (2024)

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Type of publication:

Conference abstract

Author(s):

*Jones A.; *Basavaraju N.; *Cane C.; *Kumar A.; *Moulik P.;

Citation:

Diabetes Technology and Therapeutics. Conference: Advanced Techologies and Treatments for Diabetes Conference, ATTD 2024. Virtual. 26(Supplement 2) (pp A230), 2024. Date of Publication: 01 Feb 2024.

Abstract:

Background and Aims: We assessed impact of CGM in existing CSII patients with T1D switching to hybrid closed loop (HCL), partial closed loop (PCL) or remaining on non-closed loop (NCL) CSII. Method(s): Outcomes of patients with T1D on CSII in an adult service from 2011 were reviewed. Analysis of %Time in range (%TIR), %hypoglycaemia (%hypo) and HbA1c was done with SPSS. Result(s): 302 patients were included. 183 were on Tandem T-Slim(T-Slim), 58 Omnipod Dash(DASH), 39 Medtronic780G(780G), 11 Medtronic670G(670G), and 7 Medtronic640G(640G). 218 were on HCL, 21 PCL and 63 NCL. All were on either real-time (rt)CGM (DexcomG6, GuardianG3 or GuardianG4) or intermittently scanned (is)CGM (Freestyle Libre2). T-Slim, DASH, 780G, 670G, 640G showed mean HbA1c of 53.8, 55.6, 53.0, 62, 52.8mmol/mol; %TIR of 70, 64, 72, 61, 56%; and %hypo of 1.7, 1.8, 2.0, 1.4, 4.0% respectively. Post-hoc analysis only showed statistically significant benefits with HbA1c for T-Slim over 670G, and 780G over 670G; %TIR for 780G over 640G and %hypo for T-Slim over 640G. Mean HbA1c and %TIR were significantly better on HCL vs NCL and PCL, but not %hypo. PCL did not show benefit over NCL in HbA1c, %TIR or %hypo. Conclusion(s): We propose CGM confers the most important interventional benefit in patients already on CSII. HCL provided additional benefits in improving glycaemia, both TIR and HbA1c, but not hypo in patients on CGM. PCL does not provide additional benefits over NCL in patients on CGM. QOL indices, however, may show additional benefits both in HCL and PCL.