Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review

The approval of once daily liraglutide, 3.0 mg, and once weekly semaglutide, 2.4 mg, for chronic weight management provides a novel effective strategy against obesity. The reliable models that might predict weight reducing potential at the individual level have not been identified yet. However, the coexistence of diabetes has been consistently related with less effective response than in people without this comorbidity. We aimed to review the efficacy of GLP-1 RAs approved for weight management in individuals with and without diabetes and discuss some potential mechanisms for consistently observed differences in efficacy between these two populations. The mean weight loss difference between GLP-1 RAs and placebo as add-on to lifestyle intervention in patients with diabetes was 4% to 6.2% compared to 6.1 to 17.4% in people without diabetes. Semaglutide compared to liraglutide resulted in greater weight loss. Some hypothetical explanations for the weaker anti-obesity response for both GLP-1 RAs in people with diabetes include the background medications that promote weight gain, the fear of hypoglycaemia inherently related to the treatment of diabetes, a decrease in glycosuria and subsequently less weight loss in diabetics, an altered microbiota in patients with obesity and diabetes and a genetic background that predispose to weight gain in patients with diabetes. Moreover, people with diabetes may have had obesity for longer and may be less adherent to exercise, which seems to potentiate the effects of GLP-1 RA. Emerging multimodal approaches combining peptides targeting receptors at different levels might therefore be of additional benefit particularly in patients with diabetes

Interplay between Oxidative Stress and Chronic Inflammation in PCOS: The Role of Genetic Variability in PCOS Risk and Treatment Responses

PCOS is often accompanied by insulin resistance, which is associated with the pathogenesis of the syndrome and increases the risk of developing the metabolic syndrome, type 2 diabetes, and cardiovascular complications. All these processes are characterized by chronic inflammation, which may be associated with an increased formation of reactive oxygen species and activation of inflammatory pathways that may further aggravate the function of pancreatic beta-cells. It has been shown that PCOS treatment improves metabolic indexes, while at the same time lowering inflammatory indicators. This chapter summarizes the latest findings about the role of oxidative stress and chronic inflammation in pathogenesis of PCOS. It also provides information on genetic variability in these pathways that may lead to interindividual differences in the risk for PCOS-related metabolic complications. Furthermore, genetic variability in these pathways may influence response to different treatment options in PCOS patients

Impact of COVID-19 Pandemic on Disease Control Status and Quality of Life of Patients with Acromegaly

Background and Objectives: Despite the best efforts of healthcare workers and the deployment of alternative healthcare delivery solutions through telemedicine, the pandemic has disrupted standard care for patients with chronic conditions. The long-lasting pandemic has also had a profound impact on the quality of life (QoL) of the majority of patients with chronic illnesses. The management of rare diseases has been particularly challenging. We aimed to evaluate the impacts that the long-lasting pandemic had on the disease control status and QoL in patients with acromegaly. Materials and Methods: Our prospective study included 34 patients from a national referral centre. The baseline SAGIT and AcroQoL results were obtained in October 2020 during the lockdown period of the SARS-CoV2 pandemic. The follow-up results were assessed during the summer of 2022 in a period without any public health restrictions. All the patients were additionally evaluated for their attitude towards preventative public health measures against SARS-CoV2 spread and required mask wearing during the pandemic. Results: By comparing assessments in 2020 during the lockdown period and 2022 post-lockdown, we observed some improvement in SAGIT subscores T and I, most likely reflecting treatment changes in a small number of patients. The global SAGIT score remained stable. QoL measurement by AcroQoL did not demonstrate any changes. There was a negative correlation between SAGIT subscore S and the AcroQoL results. We also noted that the group of patients with the most negative attitude toward public health measurements for preventing SARS-CoV2 spread had higher AcroQoL results than others. Conclusion: Our results showcase that the SARS-CoV2 pandemic, lasting over two years, did not impact the disease control status and QoL in patients with acromegaly. The cohort continued to be well controlled and without changes in QoL. We measured a relatively favourable attitude towards the public health measures to prevent the spread of SARS-CoV2; in particular, patients who had a lower QoL had more positive attitudes towards these measures

Problematika uživanja pijač z dodanim sladkorjem v Sloveniji in svetu

Pojavnost kardiometabolnih bolezni je dosegla pandemične razsežnosti, zato se čedalje večja pozornost posveča tudi z življenjskim slogom pogojenemu zdravju prebivalstva, še posebej načinu prehranjevanja in vnosu določenih skupin živil. Številne epidemiološke raziskave so dokazale, da je uživanje pijač z dodanim sladkorjem povezano z nastankom debelosti, sladkorne bolezni in srčno-žilnih bolezni, dodatno je tudi dober pokazatelj posameznikovega nezdravega življenjskega sloga. Pijače z dodanim sladkorjem so vir tako imenovanih »praznih kalorij«, ki nimajo hranilne vrednosti in predstavljajo največji dodatni vir energije in vnosa dodanih sladkorjev, še posebej fruktoze. Zmanjšanje vnosa pijač z dodanim sladkorjem dokazano vodi v znižanje telesne mase in zmanjšanje tveganja za nastanek kardiometabolnih bolezni. Uživanje pijač z dodanim sladkorjem je uvrščeno kar med 15 najpogostejših dejavnikov tveganja med kazalci nezdravega življenjskega sloga. Posledično je smiselno intenzivno ozaveščanje o pomembnosti opustitve uživanja pijač z dodanim sladkorjem, še posebej pri osebah s povečanim tveganjem za presnovne bolezni in mladih z nezdravim življenjskim slogom. V prispevku so opredeljene pijače z dodanim sladkorjem, opisana je njihova povezava z debelostjo, sladkorno boleznijo in srčno-žilnimi boleznimi ter možni zdravi nadomestki

Zaviralci SGLT-2

Zaviralci natrij-glukoznega prenašalnega sistema 2 (SGLT-2) so najnovejša skupina zdravil za zdravljenje sladkorne bolezni tipa 2, ki so v klinični uporabi zadnjih nekaj let. V proksimalnih tubulih ledvic zmanjšajo reabsorpcijo glukoze, ki se zato izloči z urinom. Zato se zniža koncentracija glukoze v krvi in nastopi ugodni vpliv na urejenost glikemije, obenem pa s tem ne povečajo tveganja za hipoglikemijo. Zaviralci SGLT-2 imajo tudi ugodne presnovne učinke, in sicer znižajo telesno maso, krvni tlak in koncentracijo sečne kisline v serumu. Upočasnijo tudi napredovanje začetne diabetične ledvične bolezni. Za nekatere predstavnike so tudi pokazali, da pomembno zmanjšujejo pojavnost srčno-žilnih dogodkov in zapletov, vendar mehanizem še ni v celoti raziskan in je predmet intenzivnega preučevanja. Redko povzročijo resne neželene učinke. V prispevku je opisan mehanizem delovanja zaviralcev SGLT-2, njihov vpliv na urejenost glikemije in drugo: presnovni učinki, vpliv na pojavnost srčno-žilnih bolezni in najpogostejši neželeni učinki ter možnosti predpisovanja zaviralcev SGLT-2 v Sloveniji

Effect of Oral Semaglutide on Cardiovascular Parameters and Their Mechanisms in Patients with Type 2 Diabetes: Rationale and Design of the Semaglutide Anti-Atherosclerotic Mechanisms of Action Study (SAMAS)

Introduction Type 2 diabetes (T2D) management has reached a point where not only optimal glycaemic control is necessary, but also additional interventions with proven cardiovascular risk reduction benefit. Subcutaneous semaglutide has been shown to provide cardiovascular protection, but its use may be limited by its injection formulation. To overcome this limitation, an oral semaglutide tablet has been developed, which could potentially be of the same value as its injection counterpart, but in a much wider group of patients with T2D, thereby allowing for broader cardiovascular risk reduction in this vulnerable patient population. Methods A total of 100 consecutive patients with T2D and a disease duration of up to 10 years, without manifest cardiovascular disease, who are treated with metformin (+/- sulphonylurea) and optimal cardioprotective therapy, will be recruited in a single-blinded, randomized trial named "Semaglutide Anti-atherosclerotic Mechanisms of Action Study (SAMAS)." After 1:1 randomization, patients will receive either oral semaglutide 14 mg daily or placebo for 1 year. The primary outcome comprises changes in atherosclerosis-related structural and functional characteristics of the arterial wall, namely: reduction of the carotid intima-media thickness, improvement of endothelial function and decrease in arterial stiffness. Secondary outcomes are changes in atherogenic small dense low-density lipoproteins, glucose control (HbA1c) and inflammatory markers (hsCRP). Possible correlations between primary endpoints and changes in lipids, HbA1c and high-sensitivity C-reactive protein will be sought. Discussion This is the first study to investigate the direct and indirect anti-atherosclerotic mechanisms of oral semaglutide. The results are expected to confirm the position of oral semaglutide in the multifactorial management of T2D with an emphasis on cardiovascular disease prevention

Individualizacija magistralnog hormonskog liječenja kod bolesnice s kemoterapijom induciranom prijevremenom insuficijencijom jajnika i smanjenom jetrenom funkcijom: prikaz slučaja

Although the use of commercially manufactured hormone therapy (HT) to treat menopausal symptoms has declined during the past 12 years, the use of custom compounded HT seems to have increased. A 39-year-old woman with refractory anemia sustained premature ovarian insufficiency following allogeneic stem cell transplantation. After systemic biologic treatment (azacitidine) and corticosteroid therapy, besides extreme climacteric symptoms (Green Climacteric Scale, 59) and impaired quality of life, she also had elevated liver enzymes. Therefore, she was not a candidate for oral HT. Treatment was started with 17-beta estradiol patch 0.5 mg (Climara) together with micronized progesterone intravaginally, 2x100 mg (Utrogestan) for 3 months. She was not satisfied, so the custom compound HT started with 17-beta estradiol 0.5 mg gel 2x/day and micronized progesterone in liposomal gel 100 mg/daily. She was much better but she complained of low libido, decreased sex drive and emotional instability, so 1% testosterone gel was added. Now she was completely satisfied, Green Climacteric Scale was 8 and liver enzymes were normal. In conclusion, custom compound HT has the possibility of tailoring and adjusting therapy to the individual need, which has been the everlasting goal in menopause medicine and should be a good option for special clinical cases.Premda je upotreba komercijalno pripravljene hormonske terapije u liječenju klimakteričnih simptoma u posljednjih 12 godina u padu, čini se da je upotreba magistralnih hormonskih pripravaka u porastu. Žena u dobi od 39 godina s refraktornom anemijom doživjela je prijevremenu insuficijenciju jajnika nakon transplantacije matičnih stanica. Nakon sistemskog biološkog liječenja azacitidinom i kortikosteroidima, uz izrazite klimakterične tegobe (Greenov indeks 59) i smanjenu kvalitetu života imala je povišene jetrene enzime. Zbog toga nije bila kandidat za oralnu hormonsku terapiju. Započeto je liječenje 17-beta estradiolom u obliku naljepka od 0,5 mg (Climara) zajedno s mikroniziranim progesteronom intravaginalno 2x100 mg (Utrogestan) kroz 3 mjeseca. Nije bila zadovoljna terapijom pa su joj propisani magistralno pripravljeni hormoni. Započelo se s primjenom 17-beta estradiola u obliku 0,5 mg gela 2x/dan i mikroniziranog progesterona u liposomalnom gelu 100 mg/dnevno. Bolje se je osjećala, ali još uvijek se žalila na smanjeni libido i emocionalnu nestabilnost pa je dodan 1% testosteron. Sad je bila potpuno zadovoljna terapijom, Greenova klimakterijska ljestvica bila je 8, a jetreni enzimi su se normalizirali. U zaključku, magistralni hormonski pripravci pružaju mogućnost titracije i prilagođavanja terapije individualnim potrebama, što je stalni cilj u menopauzalnoj medicini i mogao bi biti dobra mogućnost za posebne slučajeve

Glucagon-Like Peptide-1 Receptor Agonists and Dual Glucose-Dependent Insulinotropic Polypeptide/Glucagon-Like Peptide-1 Receptor Agonists in the Treatment of Obesity/Metabolic Syndrome, Prediabetes/Diabetes and Non-Alcoholic Fatty Liver Disease-Current Evidence

The obesity pandemic is accompanied by increased risk of developing metabolic syndrome (MetS) and related conditions: non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH), type 2 diabetes mellitus (T2DM) and cardiovascular (CV) disease (CVD). Lifestyle, as well as an imbalance of energy intake/expenditure, genetic predisposition, and epigenetics could lead to a dysmetabolic milieu, which is the cornerstone for the development of cardiometabolic complications. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RAs promote positive effects on most components of the "cardiometabolic continuum " and consequently help reduce the need for polypharmacy. In this review, we highlight the main pathophysiological mechanisms and risk factors (RFs), that could be controlled by GLP-1 and dual GIP/GLP-1 RAs independently or through synergism or differences in their mode of action. We also address the evidence on the use of GLP-1 and dual GIP/GLP-1 RAs in the treatment of obesity, MetS and its related conditions (prediabetes, T2DM and NAFLD/NASH). In conclusion, GLP-1 RAs have already been established for the treatment of T2DM, obesity and cardioprotection in T2DM patients, while dual GIP/GLP-1 RAs appear to have the potential to possibly surpass them for the same indications. However, their use in the prevention of T2DM and the treatment of complex cardiometabolic metabolic diseases, such as NAFLD/NASH or other metabolic disorders, would benefit from more evidence and a thorough clinical patient-centered approach. There is a need to identify those patients in whom the metabolic component predominates, and whether the benefits outweigh any potential harm

Kognitivne motnje pri bolnikih s sladkorno boleznijo tipa 2

Prevalenci sladkorne bolezni in demence v zadnjih letih naraščata, bolezni pa si delita številne dejavnike tveganja, kot so hipertenzija, dislipidemija, čezmerna telesna teža, nezdrava prehrana in telesna neaktivnost. Pomanjkanje glikemičnega nadzora se povezuje z višjim tveganjem za kognitivni upad, mikrožilni in makrožilni zapleti sladkorne bolezni pa z višjim tveganjem za razvoj demence. Bolniki s sladkorno boleznijo imajo oškodovane različne kognitivne domene. Posebej izrazite so težave na področju spomina in izvršilnih funkcij. Tovrstne težave lahko vplivajo na potek sladkorne bolezni, posameznikove možnosti uvida v lastno bolezen in sposobnosti sledenja režimu zdravljenja. Kognitivne motnje pri bolnikih s sladkorno boleznijo se povezujejo s slabšim znanjem in slabšo skrbjo za lastno bolezen, pogostejšimi napakami pri spremljanju krvne glukoze in odmerjanju inzulinskih injekcij, pogosteje zamujenimi zdravstvenimi pregledi in večjim številom epizod hipoglikemije ter srčnožilnih zapletov. Pomembno je, da pri bolnikih s sladkorno boleznijo prepoznamo kognitivne težave in jih upoštevamo pri načrtovanju zdravljenja; opredelitvi tarčnih vrednosti, edukaciji, izbiri farmakoloških in nefarmakoloških načinov zdravljenja ter nudenju podpore bolnikom in njihovim svojcem oziroma skrbnikom. Pomembni so individualni pristop, postopno uvajanje sprememb in čim bolj enostaven protokol zdravljenja (npr. uporaba zdravil s podaljšanim učinkom, uporaba razdelilcev zdravil), ki upoštevajo tudi socialno situacijo posameznika

Translating recent results from the Cardiovascular Outcomes Trials into clinical practice: recommendations from the Central and Eastern European Diabetes Expert Group (CEEDEG)

Aims: These recommendations aim to improve care for patients with type 2 diabetes (T2D) at high cardiovascular (CV) risk in Central and Eastern Europe. Cardiovascular disease (CVD) and/or chronic kidney disease (CKD) are major interdependent comorbidities in patients with T2D, accounting for 50% of mortality. Following recent CV outcomes trial (CVOT) results, including those from EMPA-REG -OUTCOME (R), LEADER (R), SUSTAIN (TM)-6 and, most recently, the CANVAS study, it is essential to develop regional expert consensus recommendations to aid physicians in interpreting these newest data to clinical practice. Methods: The Central and Eastern European Diabetes Expert Group (CEEDEG) followed a Delphi method to develop treatment algorithms to aid physicians in the clinical management of patients with T2D at high CV risk. Results: In light of the latest CVOT results, and in particular the EMPA-REG -OUTCOME (R) and -LEADER (R) trials, the diagnosis, assessment, treatment choice and monitoring of patients with T2D and established CVD and/or CKD have been considered together with existing guidelines and presented in two reference algorithms. In addition, adherence, special prescribing considerations and a proposed multidisciplinary management approach have been discussed and are presented with the proposed algorithms. Conclusions: The latest available high-level evidence on glucose-lowering drugs has enabled CEEDEG to develop practical consensus recommendations for patients with established CVD and/ or CKD. These recommendations represent an update to international and country-level guidelines used for these patients, with the aim of providing a resource not only to endocrinologists, but to cardiologists, nephrologists and primary care physicians in the region