BACKGROUND: Alzheimer\'s disease (AD) is a widespread neurological illness in the elderly, which impacted about 50 million people globally in 2020. Type 2 diabetes has been identified as a risk factor. Insulin and incretins are substances that have various impacts on neurodegenerative processes. Preclinical research has shown that GLP-1 receptor agonists decrease neuroinflammation, tau phosphorylation, amyloid deposition, synaptic function, and memory formation. Phase 2 and 3 studies are now occurring in Alzheimer\'s disease populations. In this article, we present a detailed assessment of the therapeutic potential of GLP-1 analogues and DPP4 inhibitors in Alzheimer\'s disease.
OBJECTIVE: This study aimed to gain insight into how GLP-1 analogues and associated antagonists of DPP4 safeguard against AD.
METHODS: This study uses terms from search engines, such as Scopus, PubMed, and Google Scholar, to explore the role, function, and treatment options of the GLP-1 analogue for AD.
RESULTS: The review suggested that GLP-1 analogues may be useful for treating AD because they have been linked to anti-inflammatory, neurotrophic, and neuroprotective characteristics. Throughout this review, we discuss the underlying causes of AD and how GLP signaling functions.
CONCLUSIONS: With a focus on AD, the molecular and pharmacological effects of a few GLP-1/GIP analogs, both synthetic and natural, as well as DPP4 inhibitors, have been mentioned, which are in the preclinical and clinical studies. This has been demonstrated to improve cognitive function in Alzheimer\'s patients.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a worldwide socioeconomic burden, and is accompanied by a variety of metabolic disorders, as well as nerve dysfunction referred to as diabetic neuropathy (DN). Despite a tremendous body of research, the pathogenesis of DN remains largely elusive. Currently, two schools of thought exist regarding the pathogenesis of diabetic neuropathy: a) mitochondrial-induced toxicity, and b) microvascular damage. Both mechanisms signify DN as an intractable disease and, as a consequence, therapeutic approaches treat symptoms with limited efficacy and risk of side effects.
OBJECTIVE: Here, we propose that the human body exclusively employs mechanisms of adaptation to protect itself during an adverse event. For this purpose, two control systems are defined, namely the autonomic and the neural control systems. The autonomic control system responds via inflammatory and immune responses, while the neural control system regulates neural signaling, via plastic adaptation. Both systems are proposed to regulate a network of temporal and causative connections which unravel the complex nature of diabetic complications.
RESULTS: A significant result of this approach infers that both systems make DN reversible, thus opening the door to novel therapeutic applications.

BACKGROUND: Type 2 Diabetes Mellitus (T2DM) is usually accompanied by various micro and macro vascular complications. Peripheral Arterial Disease (PAD) is one of the major complications of diabetes which is accountable for morbidity and mortality throughout the world. The first line of treatment in these individuals is life style modification and exercise. There is a dearth of literature on effect of supervised exercise program in PAD with T2DM on quality of life, walking impairment, change in Ankle Brachial Index (ABI) values. So, we conducted a systematic review to explore the available literature on supervised exercise program in PAD with T2DM.
METHODS: We conducted a systematic review (PubMed, Web of Science, CINAHL and Cochrane) to summarise the evidence on a supervised exercise program in PAD with T2DM. Randomised and nonrandomised studies were included in the review.
RESULTS: Three studies met the inclusion criteria. The outcomes taken into accounts by the studies were the quality of life, walking impairment questionnaire, Ankle brachial index. Neither of the studies matched in their supervised exercise program nor in their outcome.
CONCLUSIONS: In conclusion, the data evaluating the supervised exercise program in PAD with T2DM is inadequate to determine its effect on this population. Future large-scale studies can be conducted on both subjective and objective outcomes of PAD with T2DM to have a better understanding of the condition and for a universally acceptable exercise program for these individuals which the healthcare practitioners can use in their practice. Prospero registration number: CRD42018112465.

BACKGROUND: Thiazolidinediones are a group of synthetic medications used in type 2 diabetes treatment. Among available thiazolidinediones, pioglitazone is gaining increased attention due to its lower cardiovascular risk in type 2 diabetes mellitus sufferers and seems a promising future therapy. Accumulating evidence suggests that diabetic patients may exert bone fractures due to such treatments. Simultaneously, the female population is thought to be at greater risk. Still, the safety outcomes of pioglitazone treatment especially in terms of fractures are questionable and need to be clarified.
METHODS: We searched MEDLINE, Scopus, PsyInfo, eLIBRARY.ru electronic databases and clinical trial registries for studies reporting an association between pioglitazone and bone fractures in type 2 diabetes mellitus patients published before Feb 15, 2016. Among 1536 sources that were initially identified, six studies including 3172 patients proved relevant for further analysis.
RESULTS: Pooled analysis of the included studies demonstrated that after treatment with pioglitazone patients with type 2 diabetes mellitus had no significant increase in fracture risk [odds ratio (OR): 1.18, 95% confidence interval (CI): 0.82 to 1.71, p=0.38] compared to other antidiabetic drugs or placebo. Additionally, no association was found between the risk of fractures and pioglitazone therapy duration. The gender of the patients involved was not relevant to the risk of fractures, too.
CONCLUSIONS: Pioglitazone treatment in diabetic patients does not increase the incidence of bone fractures. Moreover, there is no significant association between patients\' fractures, their gender and the period of exposure to pioglitazone. Additional longitudinal studies need to be undertaken to obtain more detailed information on bone fragility and pioglitazone therapy.

BACKGROUND: The global epidemic of obesity will see normal weight adults constituting a mere one-third of the global population by 2025. Although appetite and weight are regulated by a complex integration of neurological, endocrine and gastrointestinal feedback mechanisms, there is a constant interaction between psychological state, physical impairment, presence of comorbid chronic disease and medications.
METHODS: We discuss two cases and reveal a practical approach to investigating and managing patients with obesity and diabetes in the \'real world\'. Within this scope, the aetiology, associated disease burden, and pharmacological therapies for the treatment of the obese patient with type 2 diabetes are reviewed. An insight into non-surgical metabolic rehabilitation is also provided.
CONCLUSIONS: Lifestyle, including diet, exercise, medications, as well as genetic predisposition, and rarely, endocrinopathies should be considered in the assessment of the obese patient. Investigations are not complex and include cardiometabolic and nutritional screens and an assessment for institution of graded, safe levels of exercise. In more complicated patients, referral to a multidisciplinary outpatient program may be necessary and it is not uncommon for patients to lose between 10-20% of their initial weight. Despite this, metabolic surgery may be necessary as further weight loss with long-term weight maintenance may be medically indicated. The type of surgery is tailored to the patient\'s medical risk and co-morbidities as well as likelihood of compliance with the required follow-up.
CONCLUSIONS: It is the opinion of the authors that metabolic rehabilitation should be intensive, multidisciplinary, and have a supervised exercise program, as the gold standard of care. These suggestions are based on the clinical pearls gained over two decades of clinical experience working in one of Australia\'s most innovative multidisciplinary metabolic rehabilitation programs caring for patients with severe obesity.