Table 2. Main studies evaluating pharmacological treatments for LADA.
| Study design | Drugs investigated | Study population | Main results | |
|---|---|---|---|---|
| Thunander et al. (2011) [61] | Randomized, open-label study | INS vs. diet +/− OHA (metformin and/or SU) | 37 Participants with NIDDM positive for GADA | Increased HbA1c levels in the diet +/− OHA group |
| C-peptide levels do not change between the two groups | ||||
| Zhou et al. (2005) [68] | Randomized, open-label study | RSG+INS vs. INS alone | 23 Participants with LADA, fasting C-peptide >0.3 nmol/L | Measures of β-cell function were higher in the RSG+INS group than in the INS group at 12 and 18 months follow-up |
| Kobayashi et al. (1996) [9] | Pilot randomized, open-label study | INS vs. SU | 10 Participants with NIDDM positive for ICAs | C-peptide response improved significantly in the INS group within 6 and 12 months, whereas decreased in the SU group |
| Two-hour blood glucose and HbA1 values were stable in the INS group and increased in the SU group | ||||
| Maruyama et al. (2008) [66] | Randomized, open-label study | INS vs. SU | 60 Participants positive for GADA | Progression rate to an insulin-dependent state was lower in the INS group than in the SU group after a mean follow-up of 57 months |
| Zhao et al. (2014) [72] | Pilot randomized, open-label study | SITA+INS vs. INS alone | 30 Participants with LADA | After 12 months measures of β-cell function were stable in SITA+INS group but significantly decreased in INS group compared with baseline |
| Johansen et al. (2014) [73] | Exploratory analysis of a double-blind, randomized, controlled study | LINA vs. Glibenclamide | 118 Participants with LADA | After 28, 52, and 104 weeks, fasting C-peptide levels significantly increased in LINA group but decrease in glibenclamide group compared with baseline |
| Buzzetti et al. (2016) [74] | Post hoc analysis of data pooled from five randomized, placebo-controlled, 24-week phase III studies | SAXA vs. placebo | 133 Participants positive for GADA | Saxagliptin reduced HbA1c from baseline in both GADA-positive and GADA-negative patients |
| Saxagliptin increased β-cell function from baseline in both GADA-positive and GADA-negative patients | ||||
| Jones et al. (2016) [78] | Longitudinal observational study | GLP1-RA exenatide and liraglutide) | 620 Participants with T2DM | Subjects with positive autoantibodies (GAD or IA-2) or severe insulin deficiency had markedly reduced glycemic response to GLP-1RA therapy |
| Subjects with positive autoantibodies experienced a 17% reduction in insulin dose (vs. 40% in autoantibody negative subjects, P<0.01) | ||||
| Pozzilli et al. (2018) [77] | Post hoc analysis of data pooled from three randomized phase III trials | Dulaglutide | 2,466 Participants with T2DM (188 GADA positive) | After 12 months dulaglutide decreased HbA1c and increase of β-cell function in GADA positive participants without effects on the rate of hypoglycemia |
LADA, latent autoimmune diabetes in adults; INS, insulin therapy; OHA, oral hypoglycemic agent; SU, sulfonylurea; NIDDM, non-insulin-dependent diabetes mellitus; GADA, glutamic acid decarboxylase autoantibody; HbA1c, glycosylated hemoglobin; RSG, rosiglitazone; ICA, islet cell antibody; SITA, sitagliptin; LINA, linagliptin; SAXA, saxagliptin; GLP1-RA, glucagon-like peptide 1 receptor agonist; T2DM, type 2 diabetes mellitus; GAD, glutamic acid decarboxylase; IA-2, tyrosine phosphatase IA-2.