The sodium/glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like-1 receptor agonists (GLP-1RA) are antidiabetic agents effective both in hemoglobin A1c (HbA1c) reduction (with a low risk of ...hypoglycemia) and cardiovascular event prevention. In patients with type 2 diabetes, the add-on value of combination therapy of GLP-1RA and an SGLT-2i seems promising.
To investigate whether the efficacy of GLP-1RA and SGLT-2i combination observed in randomized controlled trials translates into therapeutic benefits in the Croatian population during routine clinical practice and follow-up.
We included 200 type 2 diabetes patients with poor glycemic control and analyzed the effects of treatment intensification with (1) GLP-1RA on top of SGLT-2i, (2) SGLT-2i on top of GLP-1RA compared to (3) simultaneous addition of both agents. The primary study endpoint was the proportion of participants with HbA1c < 7.0% and/or 5% bodyweight reduction. Secondary outcomes included changes in fasting plasma glucose (FPG), prandial plasma glucose, low-density lipoprotein cholesterol, estimated glomerular filtration rate (eGFR), and cardiovascular (CV) incidents assessment over a follow-up period of 12 mo.
The majority of patients were over 65-years-old, had diabetes duration for more than 10 years. The initial body mass index was 39.41 ± 5.49 kg/m
and HbA1c 8.32 ± 1.26%. Around half of the patients in all three groups achieved target HbA1c below 7%. A more pronounced decrease in the HbA1c seen with simultaneous SGLT-2i and GLP-1RA therapy was a result of higher baseline HbA1c and not the effect of initiating combination therapy. The number of patients achieving FPG below 7.0 mmol/L was significantly higher in the SGLT-2i group (
= 0.021), and 5% weight loss was dominantly achieved in the simultaneous therapy group (
= 0.044). A composite outcome (reduction of HbA1c below 7% (53 mmol/mol) with 5% weight loss) was achieved in 32.3% of total patients included in the study. Only 18.2% of patients attained composite outcome defined as HbA1c below 7% (53 mmol/mol) with 5% weight loss and low-density lipoprotein cholesterol < 2.5 mmol/L. There were no significant differences between treatment groups. No differences were observed regarding CV incidents or eGFR according to treatment group over a follow-up period.
Combination therapy with GLP-1RA and SGLT-2i is effective in terms of metabolic control, although it remains to be determined whether simultaneous or sequential intensification is better.
Focal myositis is a rare, mostly benign disease (pseudotumor) of skeletal muscle, histopathologically characterized by interstitial myositis and tumorous enlargement of a single muscle. The etiology ...of focal myositis remains unknown; however, localized myopathy has been postulated to be caused by denervation lesions. This case report describes a patient that presented with clinical, laboratory, electromyoneurography, and magnetic resonance imaging features of focal myositis complicated with intervertebral disk protrusion in the lumbosacral spine affected with radicular distress. In most cases, focal myositic lesions show spontaneous regression, relapses are rare, and long-term prognosis is good. There is a wide spectrum of therapeutic options, from no therapy at all through nonsteroidal antirheumatics and glucocorticoids to radiotherapy, surgical excision, and immunosuppressants. In the patient presented, treatment with glucocorticoids, methotrexate, and surgical excision failed to produce satisfactory results. Clinical improvement, pain relief, and reduction in lower leg volume were only achieved by local infiltration of botulinum A toxin.
The aim of this study was to evaluate the incidence and type of adverse drug reactions (ADRs) and identify risk factors for ADRs in elderly patients within 30 days following discharge from an ...internal medicine clinic.
A prospective observational study was conducted at the Internal Medicine Clinic of University Hospital Dubrava, Zagreb, Croatia, between September 1(st) and November 30(th) 2012. Patients aged ≥ 65 years discharged from the clinic during the study period were eligible for inclusion in the study. The follow-up visit was scheduled ~ 30 days after discharge. During the visit, the patients were assessed for the occurrence of ADRs. Two independent physicians evaluated each possible ADR by using the Naranjo ADR probability scale. Multivariate logistic regression analysis was used to identify predisposing factors for ADRs.
There were 209 patients included in this study. A total of 72 ADRs were detected in 63 (30.1%) patients. The most frequent ADRs were bleeding disorders associated with warfarin therapy, followed by hypoglycemia associated with antidiabetics. Five (6.9%) ADRs, which resulted in hospital admission, were classified as serious. Multivariate logistic regression analysis indicated number of prescribed drugs ≥4 and prescription of furosemide and warfarin to be associated with increased risk of ADRs.
Our study showed that ADRs are an important cause of morbidity in elderly patients after hospital discharge. Judicious prescription of drugs and careful and frequent monitoring of drug therapy are necessary to reduce the risk of ADRs.
Methylenetetrahydrofolate reductase (MTHFR) polymorphism has been shown to be associated with the development of diabetic nephropathy in many ethnic groups. In this study, we examined the correlation ...between MTHFR C677T poly- morphism and microalbuminuria in patients with diabetes mellitus type 2 in Croatian patients. 85 patients with diabetes mellitus type 2 were recruited. Patients were classified into two groups – with and without diabetic nephropathy ac- cording to urinary albumin excretion rate in urine collected during 24 hours. The C677T genotype was determined by real-time PCR analysis. The genotype frequencies were CC 36,5%, CT 42,3% and TT 21,2% in diabetic patients without nephropathy versus CC 39,4%, CT 45,4% and TT 15,2% in those with nephropathy. There was no statistically significant difference in allele distribution between patients with nephropathy and those without (p=0,788). Our study did not show a correlation between mutations in the MTHFR gene and diabetic nephropathy in Croatian patients. Diabetic nephropathy is influenced by multiple risk factors which can modify the importance of MTHFR polymorphism in its de- velopment.
To present the case of axillary nerve neuropathy associated with valproic acid (VPA) poisoning.
A 26-year-old man was hospitalized because of a suicide attempt with VPA overdose. Toxicology analysis ...revealed high serum VPA level (2,896 µmol/L; therapeutic range: 350 - 690 µmol/L). Three days after admission, the patient complained of weakness in his right arm. Neurological examination revealed weakness of flexion and abduction of the right arm and loss of sensation in the skin over the lateral upper right arm. A nerve conduction velocity test was normal in the ulnar, radial, median, musculocutaneous, and suprascapular nerves. Compound muscle action potential showed reduced amplitude and prolonged latencies in the right axillary nerve taken from Erb's point and absent taken from distal stimulation point. Right axillary nerve paresis was diagnosed and the patient underwent a physical therapy program, which resulted in gradual recovery.
In the presented case, other possible causes of neuropathy were excluded by medical history, laboratory and radiological tests, and clinical course of the disease.The temporal relationship between the VPA poisoning and the occurrence of neuropathy supports the hypothesis of a VPA-caused axillary neuropathy. According to the Naranjo's Adverse Drug Reaction (ADR) Probability Scale, VPA-induced neuropathy was rated "probable".
VPA-induced neuropathy may be a serious ADR, but it is potentially preventable and reversible. Thus, clinicians should be aware of this rare ADR.
U ovom istraživanju promatran je učinak suplementacije fiksnom kombinacijom antioksidansa (beta-karoten, selen, vitamin C i E) na koncentracije serumskih lipida, u odnosu na brzinu postizanja ...eutiroze. Mjerenja su obavljena u bolesnika s novo otkrivenom Graves-ovom bolešću liječenih metimazolom (tiamazolom) prije početka terapije, te nakon 30 i 60 dana. Bolesnici su bili randomizirani u dvije skupine. Test skupinu sačinjavali su bolesnici koji su dodatno uzimali antioksidanse, a kontrolnu skupinu bolesnici koji su uzimali samo metimazol (tiamazol). Koncentracije ukupnog i HDL-kolesterola u serumu rasle su tijekom terapije kod bolesnika iz obje skupine (p < 0,05) no, nisu se međusobno značajno razlikovale 60 dana nakon početka terapije. Kod bolesnika test skupine, koncentracija LDL-kolesterola se značajno povećala (p < 0,005) i bila je značajno različita od one u kontrolnoj skupini (p < 0,005), 60 dana nakon početka liječenja.
Rezultati ovog istraživanja ukazuju da suplementacija s ovom kombinacijom antioksidansa nema značajnog utjecaja na promjene koncentracije serumskih lipida kod bolesnika s Graves-ovom bolešću 60 dana nakon početka terapije, s izuzetkom LDL-kolesterola. Zbog značajnog porasta koncentracije LDL-kolesterola kod bolesnika s Graves-ovom bolešću, koji su dodatno uzimali antioksidanse, potrebna su daljnja istraživanja u cilju pojašnjenja opisanih promjena.
Uvod: Hrvatsko društvo za dijabetes i bolesti metabolizma Hrvatskoga liječničkog zbora izradilo je 2011. godine prve nacionalne smjernice o prehrani, edukaciji i samokontroli te farmakološkom ...liječenju šećerne bolesti tipa 2. Sukladno povećanom broju dostupnih lijekova te novim spoznajama o učinkovitosti i sigurnosti primjene već uključenih lijekova, pokazala se potreba za obnovom postojećih smjernica za farmakološko liječenje šećerne bolesti tipa 2 u Republici Hrvatskoj. Sudionici: Kao koautori Smjernica navedeni su svi članovi Hrvatskog društva za dijabetes i bolesti metabolizma Hrvatskoga liječničkog zbora, kao i ostalih uključenih stručnih društava, koji su svojim komentarima i prijedlozima pridonijeli izradi Smjernica. Dokazi: Ove su Smjernice utemeljene na dokazima, prema sustavu GRADE (engl. Grading of Recommendations, Assessment, Development and Evaluation) koji uz razinu dokaza opisuje i snagu preporuke. Zaključci: Individualan pristup temeljen na fiziološkim principima regulacije glikemije nuždan je u liječenju osoba sa šećernom bolesti. Ciljeve liječenja i odabir medikamentne terapije treba prilagoditi oboljeloj osobi, uzimajući u obzir životnu dob, trajanje bolesti, očekivano trajanje života, rizik od hipoglikemije, komorbiditete, razvijene vaskularne i ostale komplikacije, kao i ostale čimbenike. Zbog svega navedenoga od nacionalnog je interesa imati praktične, racionalne i provedive smjernice za farmakološko liječenje šećerne bolesti tipa 2.
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