Network meta-analysis

Level 2 or 3 hypoglycemia (participants)

Type 2 diabetes (adults)

longest follow-upRecorded harmsEach dose separatelyHazard ratio (from event counts)Separate part 2 of a disconnected network

Randomized trials

Treatments

225

Participants

Events

In plain language

Across 2 trials with 225 participants, 0 of 2 treatments had a clearly better result than basal bolus insulin on level 2 or 3 hypoglycemia (participants), and for 2 the evidence could not tell them apart from basal bolus insulin. The most favorable estimate was for Dulaglutide flexible dose injection once weekly: hazard ratio (from event counts) 0.28 (95% credible interval 0.02 to 2.61).

Lower values favor the treatment. "Clearly" means the 95% credible interval excludes no difference. These are averages across trials; they do not say how any one person will respond. Not medical advice.

Network of trials

Each circle is a treatment; each line joins treatments that were randomized against each other in at least one trial.

Node area shows participants; line width shows trials comparing two treatments directly. Blue: GLP-1 receptor agonist containing treatments; grey: comparators. Hover over or tab to a node or line for details.

Effects compared with Basal bolus insulin

Hazard ratio (from event counts). Lower values favor the treatment.

Versus Basal bolus insulin, log scale. Blue: Bayesian random effects posterior median with 95% credible interval (thick) and 95% prediction interval (dashed). Amber diamond: frequentist estimate with 95% confidence interval. Hover over or tab to a row for its values.

Effects of each treatment versus Basal bolus insulin
Treatment	Bayesian HR (95% CrI)	95% prediction interval	Frequentist HR (95% CI)	Verdict
Dulaglutide flexible dose injection once weekly DULA_SC_FLEX_0p75-1p5_QW	0.28 (0.02 to 2.61)	0.02 to 3.26		Unclear
Basal insulin sglt2i OTHER_ACTIVE_basal_insulin_sglt2i	0.37 (0.10 to 1.45)	0.06 to 2.30		Unclear

Ranking

How likely each treatment is to be among the best. Rankings ignore the size of differences and their certainty, so read them with the effects above.

League table

Every treatment against every other: hazard ratio (from event counts) of the row treatment versus the column treatment, posterior median and 95% credible interval. Green: row clearly better; red: row clearly worse.

Every treatment in a row compared with every treatment in a column
Row versus column	OTHER_ACTIVE_basal_bolus_insulin	DULA_SC_FLEX_0p75-1p5_QW	OTHER_ACTIVE_basal_insulin_sglt2i
OTHER_ACTIVE_basal_bolus_insulin	OTHER_ACTIVE_basal_bolus_insulin	3.52 0.38 to 43.21	2.71 0.69 to 9.83
DULA_SC_FLEX_0p75-1p5_QW	0.28 0.02 to 2.61	DULA_SC_FLEX_0p75-1p5_QW	0.76 0.05 to 9.91
OTHER_ACTIVE_basal_insulin_sglt2i	0.37 0.10 to 1.45	1.31 0.10 to 22.08	OTHER_ACTIVE_basal_insulin_sglt2i

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 0.346 (95% CrI 0.074 to 1.525), log scale
Residual deviance: 3.9 for 4 data points
DIC: 7.8 (pD 3.9)
Largest R-hat: 1.001
Smallest ESS: bulk 3,073, tail 2,518
Divergent transitions: 0
Convergence: All criteria met
Priors: PR02 N(0, 5^2); PR05 N(0, 2.5^2); PR09 log normal(-2.1, 1.58^2) on tau^2 (Adverse events, pharm vs pharm)

Inconsistency

Do trials comparing two treatments directly agree with the indirect evidence through other treatments?

No comparison here has both direct and indirect evidence, so inconsistency cannot be checked by node splitting.

Small study effects

A comparison adjusted funnel plot: each point is one trial comparison, centered on its own network estimate. Asymmetry can signal that small trials with unfavorable results are missing.

Fewer than ten trial comparisons, too few to judge funnel plot asymmetry.

Baseline characteristics of the trials

The baseline value of each effect modifier or prognostic factor that applies here, per trial: mean or percent over arms, weighted by the number randomized. A note under a value names a stand in (a median for a mean, 100 minus the male share, Asian subgroup rows, an all Asian site list); "not reported" means no source of the trial prints it.

Baseline effect modifiers and prognostic factors per trial
Trial	Baseline HbA1c (percent) effect modifier, prognostic factor; 2 of 2	Background glucose lowering therapy (stratum S0 to S4) effect modifier, prognostic factor; 2 of 2
NCT02846233 S000236	9.99	S3
BEYOND S002277	8.57	S3

Comparability of the trials

Checked across designs (the set of treatments each trial compares) for eligibility, outcome definition and assessment, and the baseline factors above. Flags point to possible intransitivity; notes describe variation that is not tied to design.

FlagBaseline, Baseline HbA1c: design means range from 8.6 (OTHER_ACTIVE_basal_bolus_insulin vs OTHER_ACTIVE_basal_insulin_sglt2i) to 10.0 (DULA_SC_FLEX_0p75-1p5_QW vs OTHER_ACTIVE_basal_bolus_insulin) percent; threshold 0.5
FlagOutcome assessment, analysis set: confounded with design: other 1, randomized 1
FlagOutcome assessment, definition: confounded with design: any hypoglycemia, blood glucose below 70 mg/dL 1, level 1, below 70 mg/dL with symptoms or signs 1
FlagOutcome assessment, proportion method: confounded with design: not stated 1, observed 1
NoteOutcome assessment, time point: selected time points span 16 to 104.28 weeks
NoteData handling, input conversions: count_from_percent 2

Comparability items per trial
Trial	time weeks	analysis set	definition	instrument	adjudicated	proportion method	intercurrent events (discontinuation)	intercurrent events (rescue)	blinding	funding	start year	Eligibility
NCT02846233	16	randomized	any hypoglycemia, blood glucose below 70 mg/dL	not stated	not stated	not stated	not stated	not stated	open_label	non_industry	2016	age over 21; BMI 30 or more; HbA1c above 8 percent; eGFR above 45; basal plus prandial or premixed insulin
BEYOND	104.28	other	level 1, below 70 mg/dL with symptoms or signs	not stated	not stated	observed	not stated	not stated	open_label	non_industry	2019	age over 35; HbA1c above 7.5 percent; basal bolus insulin 6 months or more; eGFR 60 or more

Trial data

What each trial contributes. Arm rows give the arm value with its standard error, or events over participants; contrast rows give the hazard ratio (from event counts) on the analysis scale (log) against the trial's first row. Flags mark converted, combined or approximated inputs.

Trial data entering this analysis
Trial	Arm	Treatment	Week	Data	Events / N	Flags	Source
NCT02846233	A1	DULA_SC_FLEX_0p75-1p5_QW	16	arm, events	1 / 12		R0028441:Table 5
NCT02846233	A2	OTHER_ACTIVE_basal_bolus_insulin	16	arm, events	3 / 10		R0028441:Table 5
BEYOND	A1	OTHER_ACTIVE_basal_bolus_insulin	104.28	arm, events	25 / 101	count_from_percent	R0022468:Results
BEYOND	A3	OTHER_ACTIVE_basal_insulin_sglt2i	104.28	arm, events	10 / 102	count_from_percent	R0022468:Results

Rerun this analysis yourself

Remove treatments or trials and refit the frequentist and Bayesian models in your browser, with the same methods as the published analysis.

Open in the NMA lab