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The case highlights the importance of recognizing that GLP1-RAs, while beneficial for glycemic control in T2DM, can produce unexpected adverse reactions, including elevated tumor markers.

“GLP1-RAs can cause increased levels of tumor markers during the treatment of type 2 diabetes, highlighting the need for careful monitoring throughout therapy. It’s important to tailor antidiabetic management to each individual’s circumstances as necessary,” the researchers wrote in Diabetes & Metabolism.

GLP-1 receptor agonists are widely prescribed for managing T2DM. While various adverse reactions have been documented, the case by Hongmei Jiao, Department of Geriatrics, Peking University First Hospital, Beijing, China, and colleagues highlights a rare occurrence where a GLP1-RA resulted in significantly elevated levels of CA 19-9 without any indication of a tumor.

This case centers on a 69-year-old Han Chinese woman with a 30-year history of type 2 diabetes mellitus, referred to the clinic for significantly elevated CA 19-9 levels at 839.8 U/ml (normal upper limit: 37.0), despite the absence of symptoms. Seventeen months prior, she started treatment with dulaglutide (1.5 mg weekly) to enhance glycemic control, alongside metformin (500 mg thrice daily) and acarbose (100 mg thrice daily). This regimen improved her blood sugar levels, reduced her appetite, and stabilized her weight after a 3 kg loss.

Her clinical examination was unremarkable, with a body mass index of 21.1 kg/m² and an HbA1c level of 6.5%. Imaging revealed a cystic lesion in the pancreatic tail and a solid mass in the right adnexal region, diagnosed as a broad ligament leiomyoma. Further tests, including PET-CT, showed no significant lesions.

Due to concerns regarding the potential impact of GLP-1 receptor agonists on pancreatic health, dulaglutide was discontinued. One week later, CA 19-9 levels began to decline, reaching normal levels (33.29 U/ml) within two months. Following the cessation of dulaglutide, her appetite improved, but her glycemic control worsened, prompting the addition of insulin to her treatment plan.

The case highlights that elevated CA 19-9 levels can occur with dulaglutide use without malignancy, underscoring the need for careful monitoring of tumor markers during treatment. Notably, levels returned to normal after discontinuation, suggesting that such increases can be drug-related. This is the first report linking dulaglutide to abnormal CA 19-9 elevation in the absence of cancer, emphasizing the importance of follow-up and further investigation when faced with rising tumor markers.

“This case report highlights a rare phenomenon linked to individual variations in response to GLP-1 receptor agonist treatment. In clinical practice, it is crucial to quickly recognize such occurrences, intervene as needed, and discontinue the medication when appropriate to avoid adverse outcomes,” the researchers concluded.

Reference:

Liang, R., Fu, Z., Chen, L., Zhou, S., & Jiao, H. (2024). A very rare cause of markedly elevated CA 19–9: Glucagon-like peptide-1 receptor agonists. Diabetes & Metabolism, 50(6), 101578. https://doi.org/10.1016/j.diabet.2024.101578

“In a study involving over 20,000 patients with type 2 diabetes and nephrolithiasis, those who began treatment with SGLT-2 inhibitors had significantly fewer recurrent kidney stone events than those using GLP-1 receptor agonists or DPP-4 inhibitors. This protective benefit was especially evident in patients with active nephrolithiasis who also had gout. Additionally, SGLT-2 inhibitors were linked to a reduction in gout flare-ups,” the researchers reported.

Nephrolithiasis, commonly known as kidney stones, is a painful condition that can lead to significant morbidity. Patients with a history of kidney stones often find themselves in a cycle of recurrence, which can be exacerbated by conditions such as gout. Traditionally, treatment options for managing nephrolithiasis have been limited, focusing mainly on lifestyle modifications and pain management.

Against the above background, Natalie McCormick, Department of Medicine, Harvard Medical School, Boston, MA, USA, and colleagues conducted target trial emulations to compare the recurrence of nephrolithiasis in patients with a history of nephrolithiasis—both overall and specifically for those with concurrent gout—who start treatment with SGLT-2 inhibitors versus an active comparator.

The researchers conducted target trial emulation studies using a Canadian population database from 2014 to 2022, analyzing data from 20,146 patients with nephrolithiasis and type 2 diabetes, including those with gout. They compared the initiation of SGLT-2 inhibitors and GLP-1 receptor agonists against DPP-4 inhibitors. The primary outcome was recurrent nephrolithiasis events identified through emergency department visits and hospital admissions. Secondary outcomes included nephrolithiasis-related admissions and gout flare-ups. Data analysis utilized Poisson and Cox proportional hazards regression models to evaluate the effectiveness of SGLT-2 inhibitors in preventing kidney stones in high-risk patients.

The study led to the following findings:

• After adjusting for treatment effects, there were 1,924 recurrent nephrolithiasis events among 14,456 patients using SGLT-2 inhibitors (105.3 events per 1,000 person-years), compared to 853 events among 5,877 patients on GLP-1 receptor agonists (156.4 events per 1,000 person-years).
• The adjusted rate ratio was 0.67, indicating a rate difference of -51 events per 1,000 person-years (NNT of 20).
• For patients with recently active nephrolithiasis, the absolute rate difference was 219 events per 1,000 person-years (NNT of 5).
• The protective effect of SGLT-2 inhibitors persisted for nephrolithiasis events requiring emergency department visits or hospital admissions, with a rate ratio of 0.73 and a rate difference of -38 per 1,000 person-years (NNT of 26).
• Among patients with nephrolithiasis and gout, the rate ratio versus GLP-1 receptor agonists was 0.67 with a rate difference of -53 per 1,000 person-years (NNT of 19), and versus DPP-4 inhibitors, the rate ratio was 0.63 with a rate difference of -62 per 1,000 person-years (NNT of 16).
• SGLT-2 inhibitors were associated with fewer gout flare-ups, showing a rate ratio of 0.72 and a rate difference of -16 per 1,000 person-years compared to GLP-1 receptor agonists.
• SGLT-2 inhibitor users had a higher risk of genital infections (hazard ratio 2.2) and did not show a changed risk for osteoarthritis or appendicitis.
• Results remained consistent with propensity score overlap weighting.

“The findings from these target trial emulations indicate that SGLT-2 inhibitors could be a valuable addition to existing treatments for patients with nephrolithiasis, helping to manage both the recurrence of kidney stones and related comorbidities, such as gout,” the researchers concluded.

Reference:

McCormick N, Yokose C, Lu N, Wexler D J, Aviña-Zubieta J A, De Vera M A et al. Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors for recurrent nephrolithiasis among patients with pre-existing nephrolithiasis or gout: target trial emulation studies BMJ 2024; 387:e080035 doi:10.1136/bmj-2024-080035

Chronic low back pain (CLBP) is a common condition with substantial impact on patients, in the form of physical and emotional suffering; health care costs; productivity; and health care professional burden. Although clinical guidelines recommend use of nonpharmacologic treatments first, such as yoga, there is a gap between guidelines and implementation in clinical practice. A study was done to compare the effects of virtual yoga classes vs a wait-list control on CLBP intensity, back-related function, sleep quality, and pain medication use. Single-blinded, 24-week, 2-arm, randomized clinical trial conducted from May 3, 2022, through May 23, 2023, comparing live streamed yoga classes (the yoga now group) with a wait-list control (the yoga later group, in which participants were offered the virtual intervention after the study but without assessments) among adults with CLBP. Adults 18 to 64 years of age with CLBP were recruited from the Cleveland Clinic Employee Health Plan, a large health system self-insured health plan. Inclusion criteria included a mean LBP intensity score of at least 4 on an 11-point numerical rating scale (scores ranged from 0 to 10, with higher scores indicating worse pain) and daily back pain interference about half or more of the days. Coprimary outcomes were mean pain intensity in the previous week on the 11-point numerical rating scale and back-related function as assessed using the 23-point modified Roland Morris Disability Questionnaire ([RMDQ], with higher scores reflecting poorer function) at 12 weeks. Secondary and exploratory outcomes included these measures at 24 weeks, pain medication use, and PROMIS sleep quality assessed using the Sleep Disturbance Short Form 8a, item 1 (scores ranged from 0 to 4, with higher scores reflecting better sleep quality). Analyses followed the intention-to-treat principle. Results Among 140 participants enrolled (yoga now = 71; yoga later = 69), the mean (SD) age was 47.8 (11.7) years and most were female (113 [80.7%]) and college-educated (103 [73.5%]). Mean (SD) baseline pain intensity (5.7 [1.5]) and RMDQ ([12.1 [4.4]) scores reflected moderate back pain and impairment. At week 12, yoga now compared with yoga later had greater reductions in mean pain intensity (−1.5 [95% CI, −2.2 to −0.7] points; P < .001) and mean RMDQ (−2.8 [95% CI, −4.3 to −1.3] points; P < .001) scores. At 24 weeks, the improvements in pain (mean change, −2.3 [95% CI, −3.1 to −1.6] points; P < .001) and RMDQ (mean change, −4.6 [95% CI, −6.1 to −3.1] points; P < .001) scores were sustained. At 12 weeks, yoga now participants reported 21.4 (95% CI, 5.2-37.6) absolute percentage points less use of any analgesic medication during the past week than yoga later participants and at 24 weeks, 21.2 absolute percentage points (95% CI, 5.2%-37.3%). Improvements in sleep quality were greater for participants in yoga now than among participants in yoga later at 12 weeks (mean change, 0.4 [95% CI, 0.1-0.7] points; P = .008) and 24 weeks (mean change, 0.4 [95% CI, 0.1-0.7] points; P = .005). Results of this randomized clinical trial of 140 adults with CLBP who were members of a large health system self-insured health plan suggest that virtual yoga classes may be a feasible, safe, and effective treatment option.

Reference:

Tankha H, Gaskins D, Shallcross A, et al. Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial. JAMA Netw Open. 2024;7(11):e2442339. doi:10.1001/jamanetworkopen.2024.42339

Keywords:

Virtual, yoga, significantly, reduce, chronic low back pain, intensity, improve, back-related, function, JAMA , Tankha H, Gaskins D, Shallcross A

A study published in Frontiers in Medicine reveals that chronic rhinosinusitis with and without nasal polyps is closely correlated with asthma.

A study was done to investigate the correlation between chronic rhinosinusitis (CRS) and bronchial asthma, focusing on the CRS without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP), as well as their impact on lung function. A total of 141 patients diagnosed with chronic nasal-sinus inflammation were included in this study. Clinical data, including medical histories, nasal endoscopy scores, CT scores, symptom scores, and quality of life assessments, were collected. Results: Among the patients with CRSsNP, 23.8% had concomitant bronchial asthma. The incidence of asthma was significantly associated with the severity of sinus involvement in CRSsNP patients (p = 0.049). Pulmonary function impairment was correlated with the severity of sinus inflammation in CRSsNP patients (p = 0.019). Quality of life was significantly affected in patients with concomitant asthma and CRSsNP or CRSwNP. Chronic rhinosinusitis, both with and without nasal polyps, is closely correlated with bronchial asthma. Pulmonary function impairment is associated with the extent of inflammatory lesions in CRSsNP. Although CRSwNP does not significantly affect pulmonary function, the treatment of sinus diseases can contribute to the control of asthma.

Reference:

Kang, Jing, et al. “A Clinical Study On the Relationship Between Chronic Rhinosinusitis and Bronchial Asthma.” Frontiers in Medicine, vol. 11, 2024, p. 1388585.

Keywords:

Chronic, rhinosinusitis, without, nasal polyps, closely, correlated, asthma, reveals, study, Kang, Jing, Frontiers in Medicine

According to the study, the T-VASI and F-VASI have proven reliable and valid assessment tools that distinguish between different clinical groups and effectively track changes in patients with nonsegmental vitiligo.

“Notably, the study found that the thresholds for meaningful change are lower than those typically established in clinical trials. This indicates that T-VASI 50 and F-VASI 75 serve as conservative benchmarks, capturing improvements that are genuinely significant for patients managing nonsegmental vitiligo,” the researchers wrote.

Establishing meaningful improvement through the T-VASI and the F-VASI enhances the interpretation of results from clinical trials assessing vitiligo treatments. However, definitive and clinically significant thresholds for these measures have yet to be established. To address this knowledge gap, Khaled Ezzedine, Department of Dermatology, Hôpital Henri Mondor, Assistance Publique–Hôpitaux de Paris, Créteil, France, and colleagues aimed to evaluate the concept validity and measurement effectiveness of the T-VASI and F-VASI in patients with nonsegmental vitiligo, while also identifying thresholds for meaningful change.

For this purpose, the researchers conducted a mixed-methods study that analyzed data from a phase 2 multicenter, double-blind trial involving adult patients with nonsegmental vitiligo across 35 sites in Canada, France, Japan, and the US. Participants were randomized to receive 6-, 11-, or 22-mg/day upadacitinib or placebo for 24 weeks.

The study assessed the psychometric performance of the Total Vitiligo Area Scoring Index and Facial VASI, along with thresholds for meaningful change, using clinician- and patient-reported data. Qualitative interviews evaluated content validity and patient perceptions of meaningful repigmentation. Data analyses were conducted between March and July 2023.

The study led to the following findings:

• The psychometric analysis involved 164 participants, averaging 46 years old (63% female), while the qualitative analysis included 14 participants with an average age of 48.8 years (64% female, 36% male).
• Intraclass correlation coefficients indicated strong test-retest reliability: 0.98 for T-VASI and 0.99 for F-VASI between baseline and week 4.
• At baseline and week 24, correlations were moderate to strong: T-VASI with PhGVA-T (r = 0.63-0.65) and F-VASI with PhGVA-F (r = 0.65-0.71).
• Average VASI scores decreased with repigmentation, and least-square mean scores increased with greater improvement as measured by PhGIC-V.
• A 30% improvement in T-VASI and a 50% improvement in F-VASI scores were identified as meaningful changes from baseline to week 24.

The study validates the measurement properties of the Total Vitiligo Area Scoring Index (T-VASI) and Facial VASI (F-VASI) and highlights the clinical significance of the concepts they encompass. The randomized controlled trial data indicate that improvements of as little as 30% in T-VASI and 50% in F-VASI can be viewed as meaningful changes for patients.

“Consequently, the established thresholds of 50% improvement for T-VASI and 75% for F-VASI, as suggested by Kitchen et al., are effective for capturing patients’ perceptions of meaningful change in vitiligo treatment trials. Thus, both T-VASI and F-VASI are suitable tools for use in clinical trials focusing on patients with nonsegmental vitiligo,” the researchers concluded.

Reference:

Ezzedine K, Soliman AM, Camp HS, et al. Psychometric Properties and Meaningful Change Thresholds of the Vitiligo Area Scoring Index. JAMA Dermatol. Published online October 30, 2024. doi:10.1001/jamadermatol.2024.4534