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Open research questions in Diabetes Treatment and Management

375 unresolved questions extracted from the limitations and future-work sections of 1,021 Diabetes Treatment and Management papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • The comparative effects of GLP-1 RAs and DPP-4 inhibitors on neuropathy-related complications are unclear. No disease-modifying therapy currently exists for diabetic peripheral neuropathy.

    GLP-1 receptor agonists vs DPP-4 inhibitors and neuropathic complications in type 2 diabetes · 2026 · DOI

  • The paper identifies challenges in understanding the developmental implications of incretin-based therapies. It notes the complexity of pediatric obesity, arising from interactions among genetic susceptibility, neuroendocrine regulation, metabolic dysfunction, environmental exposures, and behavioral factors. The paper also highlights the need for durable efficacy, developmental safety, equitable access, and identification of patients most likely to benefit from these therapies.

    GLP-1 and Dual GIP/GLP-1 Receptor Agonists in Pediatric Obesity: From Neuroendocrine Mechanisms to Clinical Application · 2026 · DOI

  • long-term effects on growth, puberty, bone health, body composition, and weight maintenance remain uncertain, - direct evidence linking developmental characteristics to differences in therapeutic response remains limited, - data regarding developmental changes in receptor expression, receptor sensitivity, and tissue-specific responses in children and adolescents remain very limited

    GLP-1 and Dual GIP/GLP-1 Receptor Agonists in Pediatric Obesity: From Neuroendocrine Mechanisms to Clinical Application · 2026 · DOI

  • The potential for confounding variables to affect the association between GLP-1 RA use and pancreatitis. The need to balance the cohorts for treatment indications, pancreatitis risk factors, and demographics. The challenge of defining and measuring pancreatic outcomes, including acute pancreatitis and pancreatic cancer.

    Glucagon-like Peptide-1 Receptor Agonists Are Not Associated with Increased Risk of Acute Pancreatitis or Pancreatic Complications, Including Pancreatic Cancer, in Type 2 Diabetes: A Global Propensity-Matched Cohort Study · 2026 · DOI

  • The lack of large real-world, population-based analyses of the association between GLP-1 RA use and pancreatitis. The need for a propensity-matched cohort study design to compare the risk of acute pancreatitis and pancreatic complications between GLP-1 RA and SGLT2i initiators. The uncertainty surrounding the pancreatic safety of GLP-1 RAs.

    Glucagon-like Peptide-1 Receptor Agonists Are Not Associated with Increased Risk of Acute Pancreatitis or Pancreatic Complications, Including Pancreatic Cancer, in Type 2 Diabetes: A Global Propensity-Matched Cohort Study · 2026 · DOI

  • Small effect size of genetic variants on weight loss, - Limited data on the effect of different medical nutrition therapies and physical exercise, - Small sample size and limited duration of some studies, - Lack of clear association between age and baseline body mass index with weight loss

    Predictors of treatment response to semaglutide for weight management · 2026 · DOI

  • The gap between therapeutic efficacy and real-world acceptability of GLP-1 based therapies due to gastrointestinal adverse effects. The need for effective management of nausea and vomiting to prevent early discontinuation and optimize metabolic, cardiovascular, and weight-related benefits.

    Do no harm: managing nausea and vomiting in GLP-1 based obesity therapies · 2026 · DOI

  • The effectiveness of SGLT2 inhibitors in patients with heart failure and end-stage kidney disease remains uncertain due to their exclusion from major clinical trials. There is a need to evaluate the effectiveness of SGLT2 inhibitors in reducing one-year clinical outcomes in these patients. The study aims to fill this knowledge gap by providing evidence on the effectiveness of SGLT2 inhibitors in patients with HF and ESKD.

    Real-world effectiveness of SGLT2 inhibitors in patients with HF and ESKD: a multicenter cohort study · 2026 · DOI

  • small sample size, - potential confounding bias from baseline characteristics, - limited follow-up period of 16.3 months, - lack of data on long-term effects

    SGLT-2 inhibitors improve cardiac function in hypertrophic cardiomyopathy: a real-world propensity score-matched study · 2026 · DOI

  • further studies to evaluate the long-term effects of SGLT-2i in HCM patients, - investigation of the mechanisms underlying the benefits of SGLT-2i in HCM, - comparison of SGLT-2i with other treatments for HCM

    SGLT-2 inhibitors improve cardiac function in hypertrophic cardiomyopathy: a real-world propensity score-matched study · 2026 · DOI

  • integration of standardized imaging in future studies, - assessment of subclinical structural or functional CMP among carriers of genetic variants, - distinction between genotype-associated risk and phenotype-defined disease, - clarification of the stage of CMP at which SGLT2 inhibition may exert the greatest benefit

    Effects of SGLT2 inhibition on incident heart failure in carriers of cardiomyopathy-associated genetic variants · 2026 · DOI

  • The effect of SGLT2 inhibition on heart failure in carriers of cardiomyopathy-associated genetic variants is unknown. There is a lack of studies investigating the genetic basis of heart failure in relation to SGLT2 inhibition.

    Effects of SGLT2 inhibition on incident heart failure in carriers of cardiomyopathy-associated genetic variants · 2026 · DOI

  • Communication gaps were evident, as few participants initiated discussions and clinician outreach was rare. Participants expressed uncertainty about eligibility, long-term safety, and treatment expectations. Cost emerged as the most significant barrier to GLP-1RA adoption.

    Considering Glucagon-like Peptide-1 Receptor Agonists (GLP-1RAs) for Weight Loss: Insights from a Pragmatic Mixed-Methods Study of Patient Beliefs and Barriers · 2026 · DOI

  • the study had a limited sample size, - the interviews were conducted over a limited time period (June to November 2025), - the study only considered participants who were considering GLP-1RA therapy for weight loss

    Considering Glucagon-like Peptide-1 Receptor Agonists (GLP-1RAs) for Weight Loss: Insights from a Pragmatic Mixed-Methods Study of Patient Beliefs and Barriers · 2026 · DOI

  • Limited blood-brain barrier penetration, - Species differences in pharmacokinetics, - Variability in treatment response due to genetic and metabolic factors, - Ethical considerations and methodological heterogeneity complicate clinical translation

    GLP-1 Analogues in the Neurobiology of Addiction: Translational Insights and Therapeutic Perspectives · 2025 · DOI

  • Development of central nervous system penetrant analogues, - Personalized medicine approaches incorporating pharmacogenomics, - Rigorously designed trials in diverse populations

    GLP-1 Analogues in the Neurobiology of Addiction: Translational Insights and Therapeutic Perspectives · 2025 · DOI

  • Ongoing large-scale trials (e.g., EVOKE, ELAD) are further exploring the therapeutic impact of GLP-1RAs, - Exploration of GLP-1RAs in Lewy body disorders, - Investigation of the relationship between diabetes and cognitive decline

    GLP-1 and the Degenerating Brain: Exploring Mechanistic Insights and Therapeutic Potential · 2025 · DOI

  • Current treatments for neurodegenerative disorders are largely symptomatic with limited disease-modifying efficacy. There is an urgent need for novel therapeutic approaches that can halt or slow down disease progression.

    GLP-1 and the Degenerating Brain: Exploring Mechanistic Insights and Therapeutic Potential · 2025 · DOI

  • The gap in understanding the effects of GLP-1RAs on ocular diseases. The lack of knowledge on the multifaceted mechanisms by which GLP-1RAs exert ocular benefits. The need for clinical evidence to support the use of GLP-1RAs in ocular therapeutics.

    Unlocking the potential of GLP-1 receptor agonists in ocular therapeutics: from molecular pathways to clinical impact · 2025 · DOI

  • Further studies are needed to investigate the effect of GLP-1 RAs on bone metabolism, - Research on the interaction between GLP-1 RAs and other anti-diabetes drugs on bone health

    Use of GLP-1 receptor agonist and risk of osteoporosis among patients with type 2 diabetes: a real-world study · 2025 · DOI

  • Interindividual variability in response to GLP-1RAs is a clinical concern. Predictors of weight loss response to GLP-1RAs remain insufficiently defined. The study had to account for differences in efficacy and potential confounding between different GLP-1RAs and dosages.

    Predictive factors of body weight loss in patients with type 2 diabetes treated with GLP-1 receptor agonists: a 52-week prospective real-life study · 2025 · DOI

  • Investigation of the interplay between body composition, liver involvement, and the incretin response, - Study of the synergistic effect between metformin and GLP-1RAs, - Development of predictive tools to guide therapeutic decisions

    Predictive factors of body weight loss in patients with type 2 diabetes treated with GLP-1 receptor agonists: a 52-week prospective real-life study · 2025 · DOI

  • the effects of SGLT2is on URAT1 and GLUT9 remain controversial, - the compensatory response to negative energy balance can reduce the anticipated weight loss effect, - the efficacy of SGLT2is is heterogeneous across different patient populations

    SGLT2 inhibitors as metabolic modulators: beyond glycemic control in type 2 diabetes · 2025 · DOI

  • The complexity of GIP receptor pharmacology is a challenge. The potential adverse effects of GIP receptor antagonism, such as increased blood glucose levels and reduced bone mineral density, are a challenge. The need to understand the specific drug molecule, receptor functions, and the extent of GLP-1 receptor activation is a challenge.

    The evolution of the therapeutic concept ‘GIP receptor antagonism’ · 2025 · DOI

  • Further studies are needed to fully elucidate the long-term effects of therapeutic GIP receptor antagonism in humans, - Research is needed to understand the effects of GIP receptor inhibition or genetic loss-of-function receptor variants in humans, - Studies should investigate the clinical effect of GIP receptor antagonism and inhibition of endogenous GIP in adipose tissue, - The involvement of GIP in the central nervous system should be further explored

    The evolution of the therapeutic concept ‘GIP receptor antagonism’ · 2025 · DOI

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375 open questions have been extracted from the limitations and future-work passages of 1,021 Diabetes Treatment and Management papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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